IP Library › Granted Patent US 12,214,048
Granted Patent B2
US 12,214,048 · App. 17/569,261 · Granted Feb 4, 2025

Combination of an immune checkpoint modulator and a complex comprising a cell penetrating peptide, a cargo and a TLR peptide agonist for use in medicine

Inventors: Madiha Derouazi (Grand-Saconnex, CH); Elodie Belnoue (Geneva, CH)
Assignee: AMAL THERAPEUTICS SA
A61K47/66A61K38/17A61K38/18A61K39/00A61K39/0011A61K39/3955A61K39/464416A61K47/42A61K47/64A61K47/642A61K47/6425A61P35/00C07K2/00C07K7/06C07K7/08C07K14/475C07K16/2818C07K16/2863C07K16/2878C07K19/00C12N15/625A61K2039/505A61K2039/507A61K2039/545A61K2039/55516A61K2039/55572C07K2317/75C07K2317/76C07K2319/10C07K2319/40
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,214,048
App. No.
17/569,261
Granted
Feb 4, 2025
Kind
B2
Abstract

The present invention provides a combination of an immune checkpoint modulator and a complex comprising a cell penetrating peptide, at least one antigen or antigenic epitope, and a TLR peptide agonist for use in medicine, in particular in the prevention and/or treatment of cancer. Moreover, the present invention also provides compositions, such as a pharmaceutical compositions and vaccines, which are useful in medicine, for example in the prevention and/or treatment of cancer.

Claims (67)

1. A combination comprising:

(i) an immune checkpoint modulator, and

(ii) a complex comprising:

a) a cell penetrating peptide;

b) at least one antigen or antigenic epitope; and

c) at least one TLR peptide agonist, wherein the TLR peptide agonist is a TLR2 or TLR4 peptide agonist, and

wherein components a)-c) are covalently linked.

2. The combination according to claim 1 , wherein the complex is a recombinant polypeptide or a recombinant protein.

3. The combination according to claim 1 , wherein the cell penetrating peptide:

(i) has a length of 5 to 50 amino acids in total; and

(ii) has an amino acid sequence comprising a fragment of the minimal domain of ZEBRA, said minimal domain extending from residue 170 to residue 220 of the ZEBRA amino acid sequence according to SEQ ID NO: 3, or a variant thereof wherein zero 1, 2, 3, 4, or 5 amino acids have been substituted, deleted, and/or added without abrogating said peptide's cell penetrating ability, or a variant thereof.

4. The combination according to claim 3 , wherein the cell penetrating peptide has an amino acid sequence comprising the amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13), SEQ ID NO: 7 (CPP4/Z14), SEQ ID NO: 8 (CPP5/Z15), or SEQ ID NO: 11 (CPP8/Z18), or a variant thereof sharing at least 90% sequence identity with at least one of SEQ ID NOs: 6, 7, 8, or 11.

5. The combination according to claim 4 , wherein the cell penetrating peptide has an amino acid sequence comprising the amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13), SEQ ID NO: 7 (CPP4/Z14), SEQ ID NO: 8 (CPP5/Z15), or SEQ ID NO: 11 (CPP8/Z18).

6. The combination according to claim 4 , wherein the cell penetrating peptide has an amino acid sequence consisting of the amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13), SEQ ID NO: 7 (CPP4/Z14), SEQ ID NO: 8 (CPP5/Z15), or SEQ ID NO: 11 (CPP8/Z18).

7. The combination according to claim 1 , wherein the at least one antigen or antigenic epitope comprises at least one pathogen epitope, at least one tumor epitope, or a combination thereof.

8. The combination according to claim 1 , wherein the complex comprises more than one antigen or antigenic epitope positioned consecutively in the complex.

9. The combination according to claim 1 , wherein the at least one TLR peptide agonist comprises the amino acid sequence according to SEQ ID NO: 15 or 47 or a variant thereof sharing at least 90% sequence identity with SEQ ID NO: 15 or 47 without abrogating said peptide's TLR agonist ability.

10. The combination according to claim 9 , wherein the at least one TLR peptide agonist comprises the amino acid sequence according to SEQ ID NO: 15 or 47.

11. The combination according to claim 1 , wherein the immune checkpoint modulator is an activator or an inhibitor of one or more immune checkpoint point molecule(s) selected from the group consisting of CD27, CD28, CD40, CD122, CD137, OX40, GITR, ICOS, A2AR, B7-H3, B7-H4, BTLA, CTLA-4, IDO, KIR, LAG3, PD-1, TIM-3, VISTA, CEACAM1, GARP, PS, CSF1R, CD94/NKG2A, TDO, GITR, TNFR and FasR/DcR3; or an activator or an inhibitor of one or more ligands thereof.

12. The combination according to claim 11 , wherein the immune checkpoint modulator is an inhibitor of an inhibitory checkpoint molecule.

13. The combination according to claim 11 , wherein the immune checkpoint modulator is an activator of a stimulatory or costimulatory checkpoint molecule.

14. The combination according to claim 11 , wherein the immune checkpoint modulator is a modulator of CD40, CTLA-4, PD-L1, PD-L2, PD-1 and/or IDO.

15. The combination according to claim 11 comprising more than one immune checkpoint modulator.

16. The combination according to claim 11 , wherein the complex is a recombinant polypeptide or a recombinant protein wherein:

a) the cell penetrating peptide has an amino acid sequence comprising the amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13), SEQ ID NO: 7 (CPP4/Z14), SEQ ID NO: 8 (CPP5/Z15), or SEQ ID NO: 11 (CPP8/Z18), or a variant thereof sharing at least 90% sequence identity with at least one of SEQ ID NOs: 6, 7, 8, or 11 without abrogating said peptide's cell penetrating ability; and

b) the at least one antigen or antigenic epitope is a peptide, polypeptide or protein.

17. The combination according to claim 11 , wherein the complex is a recombinant polypeptide or a recombinant protein wherein:

a) the cell penetrating peptide has an amino acid sequence consisting of the amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13), SEQ ID NO: 7 (CPP4/Z14), SEQ ID NO: 8 (CPP5/Z15), or SEQ ID NO: 11 (CPP8/Z18), or a variant thereof sharing at least 90% sequence identity with at least one of SEQ ID NOs: 6, 7, 8, or 11 without abrogating said peptide's cell penetrating ability; and

b) the at least one antigen or antigenic epitope is a peptide, polypeptide or protein.

18. The combination according to claim 1 , wherein the at least one TLR peptide agonist consists of the amino acid sequence according to SEQ ID NO: 15 or 47 or a variant thereof sharing at least 90% sequence identity with SEQ ID NO:15 or 47 without abrogating said peptide's TLR agonist ability.

19. The combination according to claim 18 , wherein the at least one TLR peptide agonist consists of the amino acid sequence according to SEQ ID NO: 15 or 47.

20. A kit comprising:

(i) an immune checkpoint modulator; and

(ii) a complex comprising:

a) a cell penetrating peptide;

b) at least one antigen or antigenic epitope; and

c) at least one TLR peptide agonist, wherein the TLR peptide agonist is a TLR2 or TLR4 peptide agonist; and

wherein components a)-c) are covalently linked; and

(iii) a package insert or label having directions to treat cancer.

21. A pharmaceutical composition comprising:

(i) an immune checkpoint modulator; and

(ii) a complex comprising:

a) a cell penetrating peptide;

b) at least one antigen or antigenic epitope; and

c) at least one TLR peptide agonist, wherein the TLR peptide agonist is a TLR2 or TLR4 peptide agonist; and

wherein components a)-c) are covalently linked.

22. A combination comprising:

(i) an immune checkpoint modulator; and

(ii) a complex comprising:

a) a cell penetrating peptide;

b) at least one antigen or antigenic epitope; and

c) at least one TLR peptide agonist, wherein the TLR peptide agonist is a TLR2 or TLR4 peptide agonist;

wherein components a)-c) are covalently linked, and

wherein the complex is a recombinant polypeptide or a recombinant protein.

23. The combination according to claim 22 , wherein the cell penetrating peptide has an amino acid sequence comprising the amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13), SEQ ID NO: 7 (CPP4/Z14), SEQ ID NO: 8 (CPP5/Z15), or SEQ ID NO: 11 (CPP8/Z18), or a variant thereof sharing at least 90% sequence identity with at least one of SEQ ID NOs: 6, 7, 8, or 11.

24. The combination according to claim 23 , wherein the cell penetrating peptide has an amino acid sequence consisting of the amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13), SEQ ID NO: 7 (CPP4/Z14), SEQ ID NO: 8 (CPP5/Z15), or SEQ ID NO: 11 (CPP8/Z18).

25. The combination according to claim 22 , wherein the at least one antigen or antigenic epitope comprises at least one pathogen epitope, at least one tumor epitope, or a combination thereof.

26. The combination according to claim 22 , wherein the complex comprises more than one antigen or antigenic epitope positioned consecutively in the complex.

27. The combination according to claim 22 , wherein the at least one TLR peptide agonist comprises the amino acid sequence according to SEQ ID NO: 15 or 47 or a variant thereof sharing at least 90% sequence identity with SEQ ID NO:15 or 47 without abrogating said peptide's TLR agonist ability.

28. The combination according to claim 27 , wherein the at least one TLR peptide agonist consists of the amino acid sequence according to SEQ ID NO: 15 or 47.

29. The combination according to claim 22 , wherein the immune checkpoint modulator is an activator or an inhibitor of one or more immune checkpoint point molecule(s) selected from the group consisting of CD27, CD28, CD40, CD122, CD137, OX40, GITR, ICOS, A2AR, B7-H3, B7-H4, BTLA, CTLA-4, IDO, KIR, LAG3, PD-1, TIM-3, VISTA, CEACAM1, GARP, PS, CSF1R, CD94/NKG2A, TDO, GITR, TNFR and FasR/DcR3; or an activator or an inhibitor of one or more ligands thereof.

30. The combination according to claim 29 , wherein the immune checkpoint modulator is a modulator of CD40, CTLA-4, PD-L1, PD-L2, PD-1 and/or IDO.

31. The combination according to claim 29 comprising more than one immune checkpoint modulator.

32. The combination according to claim 30 , wherein:

a) the cell penetrating peptide has an amino acid sequence consisting of the amino acid sequence according to SEQ ID NO: 6 (CPP3/Z13), SEQ ID NO: 7 (CPP4/Z14), SEQ ID NO: 8 (CPP5/Z15), or SEQ ID NO: 11 (CPP8/Z18);

b) the at least one TLR peptide agonist consists of the amino acid sequence according to SEQ ID NO: 15 or 47; and

c) the at least one antigen or antigenic epitope is a peptide, polypeptide or protein.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 11, 2024
From: BELNOUE, ELODIE
To: AMAL THERAPEUTICS SA
Reel/Frame 067919/0938 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 6, 2023
From: DEROUAZI, MADIHA
To: AMAL THERAPEUTICS SA
Reel/Frame 062296/0543 →
Priority Claims (2)
WO PCT/EP2016/000472 · Mar 16, 2016 · international
WO PCT/EP2016/070264 · Aug 26, 2016 · international
Continuity (2)
Continuation 16084170
Related Publication 20220118102A1 · Apr 21, 2022
References Cited (400)
US 5811097A · Allison et al. · 1998 [cited by applicant]
US 5855887A · Allison et al. · 1999 [cited by applicant]
US 5977318A · Linsley et al. · 1999 [cited by applicant]
US 6051227A · Allison et al. · 2000 [cited by applicant]
US 6093794A · Barney et al. · 2000 [cited by applicant]
US 6207156B1 · Kuchroo et al. · 2001 [cited by applicant]
US 6337180B1 · Drouet et al. · 2002 [cited by applicant]
US 6682736B1 · Hanson et al. · 2004 [cited by applicant]
US 6984720B1 · Korman et al. · 2006 [cited by applicant]
US 7109003B2 · Hanson et al. · 2006 [cited by applicant]
US 7132281B2 · Hanson et al. · 2006 [cited by applicant]
US 8119775B2 · Moretta et al. · 2012 [cited by applicant]
US 8217149B2 · Irving et al. · 2012 [cited by applicant]
US 8795678B2 · Liang et al. · 2014 [cited by applicant]
US 9187534B2 · Derouazi et al. · 2015 [cited by applicant]
US 9657064B2 · Derouazi et al. · 2017 [cited by applicant]
US 10206986B2 · Ohlfest et al. · 2019 [cited by applicant]
US 11338027B2 · Derouazi et al. · 2022 [cited by applicant]
US 20020039581A1 · Carreno et al. · 2002 [cited by applicant]
US 20020086014A1 · Korman et al. · 2002 [cited by applicant]
US 20030105000A1 · Pero et al. · 2003 [cited by applicant]
US 20050019344A1 · Khanna et al. · 2005 [cited by applicant]
US 20050201994A1 · Korman et al. · 2005 [cited by applicant]
US 20060051372A1 · Vande Velde · 2006 [cited by applicant]
US 20070148184A1 · Straten et al. · 2007 [cited by applicant]
US 20080044407A1 · Strome et al. · 2008 [cited by applicant]
US 20090220532A1 · Leclerc et al. · 2009 [cited by applicant]
US 20090297552A1 · Aderem et al. · 2009 [cited by applicant]
US 20100029571A1 · Rammensee et al. · 2010 [cited by applicant]
US 20100133338A1 · Brown et al. · 2010 [cited by applicant]
US 20110236406A1 · Messmer et al. · 2011 [cited by applicant]
US 20120052080A1 · Okada · 2012 [cited by applicant]
US 20120070491A1 · Blais et al. · 2012 [cited by applicant]
US 20120177645A1 · Langermann et al. · 2012 [cited by applicant]
US 20120214744A1 · Bourdoulous et al. · 2012 [cited by applicant]
US 20120231030A1 · Derouazi et al. · 2012 [cited by applicant]
US 20120294796A1 · Johnson et al. · 2012 [cited by applicant]
US 20130116201A1 · Lenormand et al. · 2013 [cited by applicant]
US 20130183377A1 · Agrewala et al. · 2013 [cited by applicant]
US 20130331546A1 · Ohlfest et al. · 2013 [cited by applicant]
US 20160279212A1 · Ohlfest et al. · 2016 [cited by applicant]
US 20170313775A1 · Diaz et al. · 2017 [cited by applicant]
US 20180133205A1 · Gelormini · 2018 [cited by applicant]
US 20180133295A1 · Derouazi et al. · 2018 [cited by applicant]
US 20180133327A1 · Derouazi · 2018 [cited by applicant]
US 20180133338A1 · Derouazi et al. · 2018 [cited by applicant]
US 20180133339A1 · Derouazi et al. · 2018 [cited by applicant]
US 20190022203A1 · Lichty et al. · 2019 [cited by applicant]
US 20190175748A1 · Derouazi et al. · 2019 [cited by applicant]
US 20190255165A1 · Derouazi et al. · 2019 [cited by applicant]
US 20200000898A1 · Yee et al. · 2020 [cited by applicant]
US 20200031825A1 · Slassi et al. · 2020 [cited by applicant]
US 20200061097A1 · Iwasaki et al. · 2020 [cited by applicant]
US 20210085768A1 · Derouazi et al. · 2021 [cited by applicant]
US 20220031850A1 · Derouazi et al. · 2022 [cited by applicant]
US 20220040314A1 · Derouazi et al. · 2022 [cited by applicant]
US 20220088162A1 · Wollmann et al. · 2022 [cited by applicant]
US 20220111028A1 · Rossi et al. · 2022 [cited by applicant]
US 20220118102A1 · Derouazi et al. · 2022 [cited by applicant]
US 20220175933A1 · Derouazi et al. · 2022 [cited by applicant]
EP 1212422A2 · 2002 [cited by applicant]
EP 2320940A2 · 2011 [cited by applicant]
EP 2476440A1 · 2012 [cited by applicant]
EP 1913954B1 · 2012 [cited by applicant]
EP 3270955A1 · 2018 [cited by applicant]
JP 2006500358A · 2006 [cited by applicant]
JP 2007519612A · 2007 [cited by applicant]
JP 2008528643A · 2008 [cited by applicant]
JP 2011519834A · 2011 [cited by applicant]
JP 2015527313A · 2015 [cited by applicant]
KR 1020020079887 · 2002 [cited by applicant]
KR 101040281B1 · 2011 [cited by applicant]
WO WO1998042752A1 · 1998 [cited by applicant]
WO WO1999059615A1 · 1999 [cited by applicant]
WO WO2000037504A2 · 2000 [cited by applicant]
WO WO2001014424A2 · 2001 [cited by applicant]
WO WO2001051673A1 · 2001 [cited by applicant]
WO WO2004016241A1 · 2004 [cited by applicant]
WO WO2004035607A2 · 2004 [cited by applicant]
WO WO2005039632A1 · 2005 [cited by applicant]
WO WO2006081826A2 · 2006 [cited by applicant]
WO WO2008083174A2 · 2008 [cited by applicant]
WO WO2008132601A1 · 2008 [cited by applicant]
WO WO2008156712A1 · 2008 [cited by applicant]
WO WO2009015843A1 · 2009 [cited by applicant]
WO WO2009018500A1 · 2009 [cited by applicant]
WO WO2009044273A2 · 2009 [cited by applicant]
WO WO2009155535A2 · 2009 [cited by applicant]
WO WO2010105347A1 · 2010 [cited by applicant]
WO WO2011014438A1 · 2011 [cited by applicant]
WO WO2011036211A1 · 2011 [cited by applicant]
WO WO2011066389A1 · 2011 [cited by applicant]
WO WO2011101332A1 · 2011 [cited by applicant]
WO WO2011135222A2 · 2011 [cited by applicant]
WO 2012013326A1 · 2012 [cited by applicant]
WO WO2012048190A1 · 2012 [cited by applicant]
WO WO2012050365A2 · 2012 [cited by applicant]
WO WO2012097012A1 · 2012 [cited by applicant]
WO WO2013006490A2 · 2013 [cited by applicant]
WO WO2013025779A1 · 2013 [cited by applicant]
WO WO2013067492A1 · 2013 [cited by applicant]
WO WO2013075048A1 · 2013 [cited by applicant]
WO 2013113501A1 · 2013 [cited by applicant]
WO WO2013120073A1 · 2013 [cited by applicant]
WO WO2014009209A2 · 2014 [cited by applicant]
WO WO2014041505A1 · 2014 [cited by applicant]
WO WO2014046983A1 · 2014 [cited by applicant]
WO WO2014070663A1 · 2014 [cited by applicant]
WO WO2014165101A1 · 2014 [cited by applicant]
WO WO2015069932A1 · 2015 [cited by applicant]
WO WO2015103037A2 · 2015 [cited by applicant]
WO WO2015188197A2 · 2015 [cited by applicant]
WO WO2016070136A1 · 2016 [cited by applicant]
WO WO2016146143A1 · 2016 [cited by applicant]
WO WO2016146260A1 · 2016 [cited by applicant]
WO WO2016146261A1 · 2016 [cited by applicant]
WO WO201702345A1 · 2017 [cited by applicant]
WO WO2017089779A1 · 2017 [cited by applicant]
WO WO2017118864A1 · 2017 [cited by applicant]
WO WO2017195032A1 · 2017 [cited by applicant]
WO WO201815845A1 · 2018 [cited by applicant]
WO WO2018053508A1 · 2018 [cited by applicant]
WO WO2018055060A1 · 2018 [cited by applicant]
WO WO2018187356A2 · 2018 [cited by applicant]
WO WO2019150310A1 · 2019 [cited by applicant]
Buhl, T., et al. (2013), Internalization routes of cell-penetrating melanoma antigen peptides into human dendritic cells, [cited by applicant]
Pardoll, D. (2012), “The blockade of immune checkpoints in cancer immunotherapy”, [cited by applicant]
Zhang, T., et al. (2012), “LAH4 enhances CD8+ T cell immunity of protein/peptide-based vaccines”, [cited by applicant]
Walker, P, et al. (2016), “Cell-penetrating peptides—the Swiss Army knife of cancer vaccines”, [cited by applicant]
Aranda, F., et al. (2013), “Trial Watch: peptide vaccines in cancer therapy”, [cited by applicant]
International Search Report issued in PCT/EP2017/056034 dated May 24, 2017. [cited by applicant]
Written Opinion issued in PCT/EP2017/056034 dated May 24, 2017. [cited by applicant]
International Search Report issued in International Patent Application No. PCT/EP2016/000471 mailed Mar. 16, 2017. [cited by applicant]
Written Opinion issued in International Patent Application No. PCT/EP2016/000471, mailed Mar. 16, 2016. [cited by applicant]
Derouazi M. et al., (2015) “Novel cell-penetrating peptide-based vaccine induces robust CD4+ and CD8+ T cell-mediated antitumor immunity” Cancer Research, 75:15 3020-3031. [cited by applicant]
Minsig C. et al., (2014) “Identifying Appropriate Colorectal Cancer-Associated Antigens for the Clinical Trials” Current Colorectal Cancer Reports, 11:1 29-36. [cited by applicant]
Novellino L. et al., (2005) “A listing of human tumor antigens recognizes by T-cells: Mar. 2004 update” Cancer Immunology, 54:3 187-207. [cited by applicant]
Vigneron N. et al., (2013) “Database of T cell-defined human tumor antigens: the 2013 update” Cancer Immunity. 13:15. [cited by applicant]
International Search Report issued in International Patent Application No. PCT/EP2016/000473 mailed Jun. 17, 2016. [cited by applicant]
Reardon D. et al., (2013)“An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma” Expert Review of Vaccines 12:6 597-615. [cited by applicant]
International Search Report issued in International Patent Application No. PCT/EP2016/000470, mailed Jun. 17, 2016. [cited by applicant]
Written Opinion issued in International Patent Application No. PCT/EP2016/000470, mailed Jun. 17, 2016. [cited by applicant]
International Search Report issued in PCT/EP2015/002598, mailed Mar. 16, 2016. [cited by applicant]
Written Opinion issued in PCT/EP2015/002598, mailed Mar. 16, 2016. [cited by applicant]
Written Opinion issued in International Patent Application No. PCT/EP2016/00473, mailed Jun. 17, 2016. [cited by applicant]
Office Action dated Oct. 5, 2018 as issued in U.S. Appl. No. 15/557,651. [cited by applicant]
International Search Report and Written Opinion dated Jan. 8, 2014 issued in PCT Patent Application No. PCT/IB2013/058497. [cited by applicant]
Anton, L., et al. (1997), “MHC Class-I-Associated Peptides Produced from Endogenous Gene Products with Vastly Different Efficiencies”, [cited by applicant]
Brooks, N. et al. (2010), “Cell-penetrating peptides: Application in vaccine delivery”, [cited by applicant]
Derouazi, M., et al. (2010), “Towards an Efficient DC Vaccine by Antigenic Protein Loading Using a Novel Protein Transduction Domain”, [cited by applicant]
Durántez, M., et al. (2008), “Induction of Multiepitopic and Long-Lasting Immune Responses Against Tumour Antigens by Immunization with Peptides, DNA and Recombinant Adenoviruses Expressing Minigenes”, [cited by applicant]
Ishioka G., et al. (1999), “Utilization of MHC Class I Transgenic Mic for Development of MINIgene DNA Vaccines Encoding Multiple HLAK-Restricted CTL Epitopes”, [cited by applicant]
Mateo, L., et al. (1999), “An HLA-A2 Polyepitope Vaccine for Melanoma Immunotherapy”, [cited by applicant]
McPherson, S., et al. (2003), Resting CD8 T cells recognize β-galactosidase expressed in the immune-privileged retina and mediate autoimmune disease when activated, [cited by applicant]
NCBI Reference YP01673.1—BZLF1 [Human herpesvirus 4]—Protein—www.ncbi.nlm.nih.gov/protein/YP_401673—3 pages, 2012. [cited by applicant]
Rosenzweig, M., et al. (2001), “Induction of cytotoxic T lymphocyte and antibody responses to enhanced green fluorescent protein following transplantation of transduced CD 34+ hematopoietic cells”, [cited by applicant]
Rothe, R., et al. (2008), “Expression and Purification of ZEBRA Fusion Proteins and Applications for the Delivery of Macromolecules into Mammalian Cells”, [cited by applicant]
Rothe, R., et al. (2010), “Characterization of the Cell-penetrating Properties of the Epstein-Barr Virus ZEBRA trans-Activator”, [cited by applicant]
Rothe, R., et al. (2010), “PHD Thesis—Caractérisation de la propriété de la Protéine ZEBRA du virus Epstein-Barr á pénétrer dans les cellules”, [cited by applicant]
Scardino, A., et al. (2007), “A Polyepitope DNA Vaccine Targeted to Her-2/ErbB-2 Elicits a Broad Range of Human and Murine CTL Effectors to Protect against Tumor Challenge”, [cited by applicant]
Stubbs, A., et al. (2001), “Whole recombinant yeast vaccine activates dendritic cells and elicits protective cell-mediated immunity”, [cited by applicant]
Thomson, S., et al. (1995), “Minimal epitopes expressed in a recombinant polyepitope protein are processed and presented to CD8+ cytotoxic T cells: Implications for vaccine design”, [cited by applicant]
Thomson, S., et al. (1996), “Recombinant Polyepitope Vaccines for the Delivery of Multiple CD8 Cytotoxic T Cell Epitopes”, [cited by applicant]
Tine, J., et al. (2005), “Enhanced multiepitope-based vaccines elicit CD8+ cytotoxic T cells against both immunodominant and cryptic epitopes”, [cited by applicant]
Tünnemann, G., et al. (2006), “Cargo-dependent mode of uptake and bioavailability of TAT-Containing proteins and peptides in living cells”, [cited by applicant]
Van Montfoort, N., et al. (2009), “Antigen storage compartments in mature dendritic cells facilitate prolonged cytotoxic T lymphocyte cross-priming capacity”, [cited by applicant]
Waeckerle-Men Y., et al. (2005), “Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma”, [cited by applicant]
International Search Report and Written Opinion for PCT Application No. PCT/EP2017/073954 dated Dec. 22, 2017. [cited by applicant]
International Search Report issued in International Patent Application No. PCT/EP2016/000471, mailed Jun. 17, 2016. [cited by applicant]
Written Opinion issued in International Patent Application No. PCT/EP2016/000473, mailed Jun. 17, 2016. [cited by applicant]
Written Opinion issued in International Patent Application No. PCT/EP2016/000471. mailed Jun. 17, 2016. [cited by applicant]
Office Action dated Jul. 11, 2019 from U.S. Appl. No. 15/557,653. [cited by applicant]
Restriction Requirement from U.S. Appl. No. 15/557,649 dated Sep. 26, 2019. [cited by applicant]
Final Office Action from U.S. Appl. No. 15/557,651 dated Oct. 25, 2019. [cited by applicant]
Tacken, P.J., et al., “No Advantage of Cell-Penetrating Peptides over Receptor-Specific Antibodies in Targeting Antigen to Human Dendritic Cells for Cross-Presentation,” The Journal of Immunology 180: 7687-7696 (2008). [cited by applicant]
Yadav, M., et al., “Predicting immunogenic tumor mutations by combining mass spectrometry and exome sequencing,” Nature 515: 572-576 (2014). [cited by applicant]
Gnjatic, S., et al., “Toll-Like Receptor Agonists; Are They Good Adjuvants?,” The Cancer Journal 16(4): 382-391 (2010). [cited by applicant]
Restriction Requirement from U.S. Appl. No. 15/557,647 dated Aug. 22, 2019. [cited by applicant]
Schmitz, M., et al., “Generation of Survivin-specific CD8 [cited by applicant]
Hidekazu, K., et al., “Immunogenic enhancement and clinical effect by Type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer in patients,” Cancer Science, 102(6): 11… [cited by applicant]
Friedrichs, B., et al., “Survivin-derived peptide epitopes and their role for induction of antitumor immunity in hematological malignancies,” Leukemia & Lymphoma, 47(6): 978-985 (2006). [cited by applicant]
Non-final Office Action from U.S. Appl. No. 15/557,649 dated Feb. 3, 2020. [cited by applicant]
Office Action from U.S. Appl. No. 15/557,653 dated Apr. 13, 2020. [cited by applicant]
Oh, T., et al., “Immunocompetent murine models for the study of glioblastoma immunotherapy,” Journal of Translational Medicine, 12(107): 1-10 (2014). [cited by applicant]
Office Action issued in U.S. Appl. No. 15/557,651 dated Apr. 22, 2020. [cited by applicant]
Office Action from U.S. Appl. No. 15/557,647 dated Jun. 22, 2020. [cited by applicant]
Office Action from U.S. Appl. No. 15/557,649 dated Jul. 7, 2020. [cited by applicant]
Houot, R., and Levy, R., “T-cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy,” Blood, 113(15): 3546-3552 (2009). [cited by applicant]
Office Action issued in corresponding RU Application No. 2018135097 dated Jul. 30, 2020. [cited by applicant]
Muller, S., et al., “Nucleic Acids From A to Z,” Moscow: BINOM. Knowledge laboratory, p. 216 (2013). [cited by applicant]
Office Action from corresponding U.S. Appl. No. 15/557,653 dated Dec. 14, 2020. [cited by applicant]
Office Action from corresponding U.S. Appl. No. 16/084,170 dated Nov. 10, 2020. [cited by applicant]
Zamarin, D., and Postow, M.A., “Immune checkpoint modulation: Rational design of combination strategies,” Pharmacology & Therapeutics, 150: 23-32 (2015). [cited by applicant]
Stewart, B. and C. Wild, [cited by applicant]
Burt, R.W., J.A. DiSario, and L. Cannon-Albright, [cited by applicant]
Sieber, O.M., et al., [cited by applicant]
Lynch, H.T., et al., [cited by applicant]
Ekbom, A., et al., [cited by applicant]
Jemal, A., et al., [cited by applicant]
Moertel, C.G., [cited by applicant]
Meyerhardt, J.A. and R.J. Mayer, [cited by applicant]
Gallagher, D.J. and N. Kemeny, [cited by applicant]
Smith, C.L., et al., [cited by applicant]
Koido, S., et al., [cited by applicant]
Xiang, B., et al., [cited by applicant]
Clarke, J.M. and H.I. Hurwitz, [cited by applicant]
Siegel, R., C. Desantis, and A. Jemal, [cited by applicant]
Slingluff CL, Jr. The present and future of peptide vaccines for cancer: single or multiple, long or short, alone or in combination? Cancer journal 2011; 17(5):343-50. [cited by applicant]
Melief CJ, van der Burg SH. Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines. Nature reviews Cancer 2008;8(5):351-60. [cited by applicant]
Kruit WH, Suciu S, Dreno B, Mortier L, Robert C, Chiarion-Sileni V, et al. Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: results of a randomized phase II study of the European Organisat… [cited by applicant]
Vansteenkiste J, Zielinski M, Linder A, Dahabreh J, Gonzalez EE, Malinowski W, et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results. Journal of clinical oncolog… [cited by applicant]
Toes RE, Offringa R, Blom RJ, Melief CJ, Kast WM. Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction. Proceedings of the National Academy of Sciences of the United States o… [cited by applicant]
Rosalia RA, Quakkelaar ED, Redeker A, Khan S, Camps M, Drijfhout JW, et al. Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation. European journ… [cited by applicant]
Apetoh L, Locher C, Ghiringhelli F, Kroemer G, Zitvogel L. Harnessing dendritic cells in cancer. Semin Immunol. 2011; 23:42-49. [cited by applicant]
Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998; 392:245-252. [cited by applicant]
Wang RF, Wang HY. Enhancement of antitumor immunity by prolonging antigen presentation on dendritic cells. Nat Biotechnol. 2002; 20:149-156. [cited by applicant]
Copolovici DM, Langel K, Eriste E, Langel U. Cell-penetrating peptides: design, synthesis, and applications. ACS nano 2014;8(3):1972-94. [cited by applicant]
Milletti, F., Cell-penetrating peptides: classes, origin, and current landscape. Drug Discov Today 17 (15-16): 850-60, 2012. [cited by applicant]
Berry CC. Intracellular delivery of nanoparticles via the HIV-1 tat peptide. Nanomedicine. 2008, 3:357-365. [cited by applicant]
Deshayes S, Morris MC, Divita G, Heitz F. Cell-penetrating peptides: Tools for intracellular delivery of therapeutics. Cell Mol Life Sci. 2005; 62:1839-1849. [cited by applicant]
Edenhofer F. Protein transduction revisited: Novel insights into the mechanism underlying intracellular delivery of proteins. Curr Pharm Des. 2008; 14:3628-3636. [cited by applicant]
Gupta B, Levchenko TS, Torchilin VP. Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv Drug Deliv Rev. 2005; 57:637-651. [cited by applicant]
Torchilin VP. Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annu Rev Biomed Eng. 2006; 8:343-375. [cited by applicant]
Wang HY, Fu T, Wang G, Gang Z, Donna MPL, Yang JC, Restifo NP, Hwu P, Wang RF. Induction of CD4+ T cell-dependent antitumor immunity by TAT-mediated tumor antigen delivery into dendritic cells. J Clin Invest. 2002a; 109… [cited by applicant]
Frankel, A.D. and C.O. Pabo, Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 1988. 55(6): p. 1189-93. [cited by applicant]
Joliot, A., et al., Antennapedia homeobox peptide regulates neural morphogenesis. Proc Natl Acad Sci U S A, 1991. 88(5): p. 1864-8. [cited by applicant]
Derossi, D., et al., The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem, 1994. 269(14): p. 10444-50. [cited by applicant]
Vives, E., P. Brodin, and B. Lebleu, A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus. J Biol Chem, 1997. 272(25): p. 16010-7. [cited by applicant]
Elliott, G. and P. O'Hare, Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell, 1997. 88(2): p. 223-33. [cited by applicant]
Dempsey, C.E., The actions of melittin on membranes. Biochim Biophys Acta, 1990. 1031 (2): p. 143-61. [cited by applicant]
Konno, K., et al., Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp ( [cited by applicant]
Esteve, E., et al., Transduction of the scorpion toxin maurocalcine into cells. Evidence that the toxin crosses the plasma membrane. J Biol Chem, 2005. 280(13): p. 12833-9. [cited by applicant]
Nascimento, F.D., et al., Crotamine mediates gene delivery into cells through the binding to heparan sulfate proteoglycans. J Biol Chem, 2007. 282(29): p. 21349-60. [cited by applicant]
Kobayashi, S., et al., Membrane translocation mechanism of the antimicrobial peptide buforin 2. Biochemistry, 2004. 43(49): p. 15610-6. [cited by applicant]
Futaki, S., et al., Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem, 2001. 276(8): p. 5836-40. [cited by applicant]
Pooga, M., et al., Cell penetration by transportion. FASEB J, 1998. 12(1): p. 67-77. [cited by applicant]
Nair et al. (2003, Nucleic Acids Res. 31(1): 397-399. [cited by applicant]
Kapoor et al. (2012, PLoS ONE 7(4): e35187. [cited by applicant]
Lim, Y.T., Vaccine adjuvant materials for cancer immunotherapy and control of infectious disease. Clin Exp Vaccine Res, 2015. 4(1): p. 54-8. [cited by applicant]
Baxevanis, C.N., I.F. Voutsas, and O.E. Tsitsilonis, Toll-like receptor agonists: current status and future perspective on their utility as adjuvants in improving anticancer vaccination strategies. Immunotherapy, 2013. … [cited by applicant]
Duthie MS, Windish HP, Fox CB, Reed SG. Use of defined TLR ligands as adjuvants within human vaccines. Immunol Rev. 2011; 239:178-196. [cited by applicant]
Manicassamy S, Pulendran B. Modulation of adaptive immunity with Toll-like receptors. Semin Immunol. 2009; 21:185-193. [cited by applicant]
Zom GG, Khan S, Filippov DV, Ossendorp F. TLR ligand-peptide conjugate vaccines: toward clinical application. Adv Immunol. 2012;114:177-201. [cited by applicant]
Fujita, Y. and H. Taguchi, [cited by applicant]
Monie, T. P., Bryant, C. E., et al. 2009: Activating immunity: Lessons from the TLRs and NLRs. Trends Biochem. Sci. 34(11), 553-561. [cited by applicant]
Gay, N. J., and Gangloff, M. (2007): Structure and function of Toll receptors and their ligands. Annu. Rev. Biochem. 76, 141-165. [cited by applicant]
Spohn, R., Buwitt-Beckmann, U., et al. (2004): Synthetic lipopeptide adjuvants and Toll-like receptor 2-Structure-activity relationships. Vaccine 22(19), 2494-2499. [cited by applicant]
Bryant, C. E., Spring, D. R., et al. (2010). The molecular basis of the host response to lipopolysaccharide. Nat. Rev. Microbiol. 8(1), 8-14. [cited by applicant]
Barbalat R, Lau L, Locksley RM, Barton GM. Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nat Immunol. 2009: 10(11):1200-7. [cited by applicant]
Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. Feb. 24; 2006: 124(4):783-801. [cited by applicant]
Kumar H, Kawai T, Akira S. Toll-like receptors and innate immunity. Biochem Biophys Res Commun. Oct. 30; 2009 388(4):621-5. [cited by applicant]
Lasarte, J.J., et al., The extra domain A from fibronectin targets antigens to TLR4-expressing cells and induces cytotoxic T cell responses in vivo. J Immunol, 2007. 178(2): p. 748-56. [cited by applicant]
Applequist, S.E., R.P. Wallin, and H.G. Ljunggren, Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines. Int Immunol, 2002. 14(9): p. 1065-74. [cited by applicant]
Okamura, Y., et al., The extra domain A of fibronectin activates Toll-like receptor 4. J Biol Chem, 2001. 276(13): p. 10229-33. [cited by applicant]
Jameson et al., Nature, 368,744-746 (1994). [cited by applicant]
Brady et al., Nature, 368,692-693 (1994). [cited by applicant]
Seifter et al. (1990) Analysis for protein modifications and nonprotein cofactors, Meth. Enzymol. 182: 626-646. [cited by applicant]
Rattan et al., (1992) Protein Synthesis: Post-translational Modifications and Aging, Ann NY Acad Sci, 663: 48-62. [cited by applicant]
Karlin et al. (1993), PNAS USA, 90:5873-5877. [cited by applicant]
Altschul et al., 1990, J. Mol. Biol. 215, 403-410. [cited by applicant]
Altschul et al. (1997), Nucleic Acids Res, 25:3389-3402. [cited by applicant]
Pearson (1990), Methods Enzymol. 183, 63-98. [cited by applicant]
Pearson and Lipman (1988), Proc. Natl. Acad. Sci. U. S. A 85, 2444-2448. [cited by applicant]
Devereux et al., 1984, Nucleic Acids Res., 387-395. [cited by applicant]
Smith and Waterman (1981), J. Mol. Biol. 147, 195-197. [cited by applicant]
Apostolopoulos et al., 1996 Immunol. Cell. Biol. 74: 457-464. [cited by applicant]
Pandey et al., 1995, Cancer Res. 55: 4000-4003. [cited by applicant]
Kierkegaard et al., 1995, Gynecol. Oncol. 59: 251-254. [cited by applicant]
Kievit et al., 1997, Int. J. Cancer 71: 237-245. [cited by applicant]
Lozza et al., 1997 Anticancer Res. 17: 525-529. [cited by applicant]
Mota et al., 1997, Am. J Pathol. 150: 1223-1229. [cited by applicant]
Fishman et al., 1997 Cancer 79: 1461-1464. [cited by applicant]
Notelet et al., 1997 Surg. Neurol. 47: 364-370. [cited by applicant]
Lucas et al., 1996 Anticancer Res. 16: 2493-2496. [cited by applicant]
Macs et al., 1996, J. Cancer Res. Clin. Oncol. 122: 296-300. [cited by applicant]
Tolliver and O'Brien, 1997, South Med. J. 90: 89-90. [cited by applicant]
Tsuruta at al., 1997 Urol. Int. 58: 20-24. [cited by applicant]
Huang et al., Exper Rev. Vaccines (2002)1:49-63. [cited by applicant]
Zantek et al., Cell Growth Differ. (1999) 10:629-38. [cited by applicant]
Carles-Kinch et al., Cancer Res. (2002) 62:2840-7. [cited by applicant]
Cheng at al., 2002, Cytokine Growth Factor Rev. 13:75-85. [cited by applicant]
Dahlenborg et al., 1997, Int. J Cancer 70: 63-71. [cited by applicant]
Zajac et al., 1997, Int. J Cancer 71: 491-496. [cited by applicant]
Deshpande and Danishefsky, 1997, Nature 387: 164-166. [cited by applicant]
Kawakami and Rosenberg, 1997, Int. Rev. Immunol. 14: 173-192. [cited by applicant]
Molldrem et al., Blood (1996) 88:2450-7. [cited by applicant]
Molldrem et al., Blood (1997) 90:2529-34. [cited by applicant]
De wit Amer 2010, Neuro Oncol, 12(3):304-16. [cited by applicant]
Maccalli, C., et al., [cited by applicant]
Derouazi M, Wang Y, Marlu R, et al. Optimal epitope composition after antigen screening using a live bacterial delivery vector: Application to TRP-2. Bioengineered Bugs. 2010;1 (1):51-60. doi:10.4161/bbug.1.1.9482. [cited by applicant]
Lu et al., Multiepitope trojan antigen peptide vaccines for the induction of antitumor CTL and Th immune responses J. Immunol., 172 (2004), pp. 4575-4582. [cited by applicant]
Rose et al. (1994), JACS 116, 30. [cited by applicant]
Means and Feeney, Chemical Modification of Proteins, Holden-Day, 1974, pp. 39-43. [cited by applicant]
Chen X. et al., 2013: Fusion Protein Linkers: Property, Design and Functionality. Adv Drug Deliv Rev. 65(10): 1357-1369. [cited by applicant]
Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria; J. Natl. Cancer Inst. 2010, 102(18): 1388-1397. [cited by applicant]
Jewell, C.M., S.C. Lopez, and D.J. Irvine, [cited by applicant]
Newcomb, E. and D. Zagzag, The murine GL261 glioma experimental model to assess novel brain tumor treatments, in CNS Cancer Models, Markers, Prognostic, Factors, Targets, and Therapeutic Approaches, E.G. Van Meir, Edito… [cited by applicant]
Jacobs, V.L., et al., Current review of in vivo GBM rodent models: emphasis on the CNS-1 tumour model. ASN Neuro, 2011. 3(3): p. e00063. [cited by applicant]
Zhu, X., et al., [cited by applicant]
Zhu, X., et al., [cited by applicant]
Ohlfest, J.R., et al., [cited by applicant]
Käll L, Canterbury JD, Weston J, Noble WS, MacCoss MJ (2007) Semi-supervised learning for peptide identification from shotgun proteomics datasets. Nat Methods 4(11):923-925. [cited by applicant]
Susumu Suzuki et al., 2016: Current status of immunotherapy. Japanese Journal of Clinical Oncology, 2016: doi: 10.1093/jjco/hyv201 [Epub ahead of print]. [cited by applicant]
Hamid et al., 2013; N. Engl. J. Med. 369: 134-144. [cited by applicant]
Brignone et al., 2009, Clin. Cancer Res. 15: 6225-6231. [cited by applicant]
Keir, M.E., et al., PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol, 2008. 26: p. 677-704. [cited by applicant]
Semakova, A.P., et al., “Adjuvant Technologies in the Construction of Advanced Vaccines”, Problems of Particularly Dangerous Infections, 2: p. 28-35 (2016). [cited by applicant]
[cited by applicant]
Stupp, R., et al., [cited by applicant]
Hegi, M.E., et al., [cited by applicant]
Bechmann, I., I. Galea, and V.H. Perry, [cited by applicant]
Walker, P.R., et al., [cited by applicant]
Hickey, W.F., B.L. Hsu, and H. Kimura, [cited by applicant]
Abou-Ghazal, M., et al., [cited by applicant]
Buckanovich, R.J., et al., [cited by applicant]
Mittelbronn, M., et al., [cited by applicant]
Perrin, G., et al., [cited by applicant]
Bucciero, A., et al., [cited by applicant]
Tang, J., et al., [cited by applicant]
Maus, M.V., et al., [cited by applicant]
Saikali, S., et al., [cited by applicant]
Schuster, J., et al., [cited by applicant]
Nakada, M., Y. Hayashi, and J. Hamada, [cited by applicant]
Phuphanich, S., et al., [cited by applicant]
Kyte and Doolittle, 1982, J. Mol. Biol. 157(1):105-132. [cited by applicant]
Cobbs CS, Harkins L, Samanta M, et al. Human cytomegalovirus infection and expression human malignant glioma. Cancer Res. 2002;62:3347-3350. [cited by applicant]
Trivedi et al., Blood, 105:2793 (2005). [cited by applicant]
Shaw, E.G., et al., [cited by applicant]
Greenspan, N.S., & Cera, E.D., “Defining epitopes: It's not as easy as it seems,” Nature Biotechnology, 17: 936-937 (1999). [cited by applicant]
Rudikoff, S., et al., “Single amino acid substitution altering antigen-binding specificity,” Proc. Natl. Acad. Sci. USA, 79: 1979-1983 (1982). [cited by applicant]
Colman, P.M., “Effects of amino acid sequence changes on antibody-antigen interactions,” Research in Immunology, 145(1): 33-36 (1994). [cited by applicant]
Wang, C.Y., et al., “Systematic analysis of the achaete-scute complex-like gene signature in clinical cancer patients”. Mol Clin Oncol., 6(1):7-18 (2017). [cited by applicant]
Zhao, M., and Weissleder, R., “Intracellular Cargo Delivery Using Tat Peptide and Derivatives,” Medicinal Research Reviews, 24(1): 1-12 (2004). [cited by applicant]
Heitz, F., et al., “Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics,” British Journal of Pharmacology, 157(2): 195-206 (2009). [cited by applicant]
Spencer, A.J., et al., “Fusion of the [cited by applicant]
Shen, J., et al., “Single Variable Domain-IgG Fusion: A Novel Recombinant Approach to Fc Domain-Containing Bispecific Antibodies”, The Journal of Biological Chemistry, 281(16), 10706-10714 (2006). [cited by applicant]
Swiech, K., et al., “Human cells: New platform for recombinant therapeutic protein production,” Protein Expression and Purification, 84(1): 147-153 (2012). [cited by applicant]
Welniak, L.A., et al., “Immunobiology of Allogeneic Hematopoietic stem cell transplantation,” Annu. Rev. Immunol., 25: 139-170 (2007). [cited by applicant]
Grupp, S.A., et al., “Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia,” New England Journal of Medicine, 368(16): 1509-1518 (2013). [cited by applicant]
Jones, H.L., et al., “Luminal Epithelial Antigen (LEA. 135) Expression Correlates with Tumor Progression for Transitional Carcinoma of the Bladder,” AntiCancer Research, 17: 685-688 (1997). [cited by applicant]
Beckett, M.L., and Wright Jr., G.L., “Characterization of a Prostate Carcinoma Mucin-Like Antigen (PMA),” Int. J. Cancer, 62: 703-710 (1995). [cited by applicant]
Antonia, Scott et al., 2016, Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study; Lancet Oncol. Feb. 5, 2016. pii: S1470-2045(15)00544-6. doi: 10.1… [cited by applicant]
Greenwald, R.J., G.J. Freeman, and A.H. Sharpe, [cited by applicant]
Zou, W. and L. Chen, Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol, 2008. 8(6): p. 467-77. [cited by applicant]
Chapoval, A.I., et al., [cited by applicant]
Sica, G.L., et al., [cited by applicant]
Loos, M., et al., [cited by applicant]
Hofmeyer, K.A., A. Ray, and X. Zang, [cited by applicant]
Sun, J., et al., [cited by applicant]
Dangaj, D. and N. Scholler, [cited by applicant]
Dangaj, D., et al., [cited by applicant]
Wang, X., et al., [cited by applicant]
Leong, S.R., et al., [cited by applicant]
Buchbinder E. I. and Desai A., 2016: CTLA-4 and PD-1 Pathways—Similarities, Differences and Implications of Their Inhibition; American Journal of Clinical Oncology, 39(1): 98-106. [cited by applicant]
Hurwitz et al., Proc. Natl. Acad. Sci. USA, 95(17):10067-10071 (1998). [cited by applicant]
Camacho et al., J. Clin. Oncology, 22(14):Abstract No. 2505 (2004). [cited by applicant]
Mokyr et al., Cancer Res., 58:5301-5304 (1998). [cited by applicant]
Jenessa B. Smith et al., 2014: B7-H4 as a potential target for immunotherapy for gynecologic cancers: A closer look. Gynecol Oncol 134(1): 181-189. [cited by applicant]
Croft, M., C.A. Benedict, and C.F. Ware, [cited by applicant]
Aggarwal, B.B., [cited by applicant]
Avogadri, F., et al., [cited by applicant]
Naidoo, J., D.B. Page, and J.D. Wolchok, [cited by applicant]
Bremer, E., [cited by applicant]
Sufia Butt Hassan, Jesper Freddie Sørensen, Barbara Nicola Olsen and Anders Elm Pedersen, 2014: Anti-CD40-mediated cancer immunotherapy: an update of recent and ongoing clinical trials, Immunopharmacology and Immunotoxi… [cited by applicant]
Alison Crawford and E. John Wherry, 2009: Editorial: Therapeutic potential of targeting BTLA. Journal of Leukocyte Biology 86: 5-8. [cited by applicant]
Hemon, P., et al., [cited by applicant]
Thielens, A., E. Vivier, and F. Romagne, [cited by applicant]
Benson et al., 2012, Blood 120:4324-4333. [cited by applicant]
Ngiow, S.F., et al., [cited by applicant]
Jones et al., 2008, J Exp Med. 205 (12): 2763-79. [cited by applicant]
Huang, Y.H., et al., [cited by applicant]
Gray-Owen, S.D. and R.S. Blumberg, [cited by applicant]
Creelan, B.C., [cited by applicant]
Yin, Y., et al., [cited by applicant]
Zhu, Y., et al., [cited by applicant]
Sheu, B.C., et al., [cited by applicant]
Tanaka, J., et al., [cited by applicant]
Ball, H.J., et al., [cited by applicant]
Liu, X., et al., [cited by applicant]
Ino, K., et al., [cited by applicant]
Muller, A.J., et al., [cited by applicant]
[cited by applicant]
Garber, K., [cited by applicant]
Platten, M., W. Wick, and B.J. Van den Eynde, [cited by applicant]
Platten, M., et al., [cited by applicant]
Robert D. Leone et al., 2015: A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy. Computational and Structural Biotechnology Journal 13: 265-272. [cited by applicant]
Woo et al., 2012, Cancer Res. 72: 917-27. [cited by applicant]
Butler N. S. et al., 2011, Nat Immunol. 13: 188-95. [cited by applicant]
Fu et al., 2011, Cancer Res. 71: 5445-54. [cited by applicant]
Curran et al., 2011, PLoS One 6(4): el 9499. [cited by applicant]
Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P, et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med. 2006; 203:871-81. [cited by applicant]
Van Dijk, M. A., and van de Winkel, J. G., [cited by applicant]
Jakobovits, A., et al., [cited by applicant]
Jakobovits, A., et al., [cited by applicant]
Bruggemann, M., et al., [cited by applicant]
Hoogenboom, H. R., and Winter, G., [cited by applicant]
Marks, J. D., et al., [cited by applicant]
Cole et al., [cited by applicant]
Boerner, P., et al., [cited by applicant]
Holliger and Hudson, 2005, [cited by applicant]