Granted Patent
B2
US 12,193,998 · App. 17/738,418 · Granted Jan 14, 2025
Peptides and combination of peptides for use in immunotherapy against various cancers
Inventors:
Andrea Mahr (Tuebingen, DE); Toni Weinschenk (Tuebingen, DE); Colette Song (Tuebingen, DE); Oliver Schoor (Tuebingen, DE); Jens Fritsche (Tuebingen, DE); Harpreet Singh (Tuebingen, DE)
Assignee:
Immatics Biotechnologies GmbH
A61K39/0011A61K35/17A61K39/4611A61K39/4644C07K7/06C07K7/08C07K14/47C07K14/4748C07K14/705C07K14/7051C07K14/71C07K14/721C07K14/8135C07K16/18C07K16/28C07K16/2863C07K16/2869C07K16/30C07K16/38C07K16/40C12N5/0636C12N5/0638C12N9/0091C12N9/1264C12N15/115C12Q1/6886C12Y116/01C12Y207/07031G01N33/57484G16B25/00G16B25/10A61K38/00A61K2039/572C07K2317/34C07K2317/76C07K2319/40C12N2310/16C12N2502/11C12Q2600/156G01N2333/47
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.
Claims (20)
1. A peptide consisting of the amino acid sequence FINDSIVYL (SEQ ID NO: 106) in the form of a pharmaceutically acceptable salt.
2. The peptide of claim 1 , wherein said peptide has the ability to bind to an MHC class-I molecule, and wherein said peptide, when bound to said MHC, is capable of being recognized by CD8 T cells.
3. The peptide of claim 1 , wherein the pharmaceutically acceptable salt is chloride salt.
4. The peptide of claim 1 , wherein the pharmaceutically acceptable salt is acetate salt.
5. A composition comprising the peptide of claim 1 and a pharmaceutically acceptable carrier.
6. The composition of claim 5 , wherein the peptide is in the form of a chloride salt.
7. The composition of claim 5 , wherein the peptide is in the form of an acetate salt.
8. The composition of claim 5 , further comprising an adjuvant selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I: C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.
9. The composition of claim 8 , wherein the adjuvant is IL-2.
10. The composition of claim 8 , wherein the adjuvant is IL-7.
11. The composition of claim 8 , wherein the adjuvant is IL-12.
12. The composition of claim 8 , wherein the adjuvant is IL-15.
13. The composition of claim 8 , wherein the adjuvant is IL-21.
14. A pegylated peptide consisting of the amino acid sequence of FINDSIVYL (SEQ ID NO: 106) or a pharmaceutically acceptable salt thereof.
15. The peptide of claim 14 , wherein the pharmaceutically acceptable salt is chloride salt.
16. The peptide of claim 14 , wherein the pharmaceutically acceptable salt is acetate salt.
17. A composition comprising the pegylated peptide of claim 14 or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
18. The composition of claim 5 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of saline, Ringer's solution, dextrose solution, and sustained release preparation.
19. The peptide in the form of a pharmaceutically acceptable salt of claim 1 , wherein said peptide is produced by solid phase peptide synthesis or produced by a yeast cell or bacterial cell expression system.
20. A composition comprising the peptide of claim 1 , wherein the composition is a pharmaceutical composition and comprises water and a buffer.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 6, 2022
From: MAHR, ANDREA; WEINSCHENK, TONI; SONG, COLETTE; SCHOOR, OLIVER; FRITSCHE, JENS; SINGH, HARPREET
To: IMMATICS BIOTECHNOLOGIES GMBH
Reel/Frame 059843/0346 →
Priority Claims (1)
GB 1521894
· Dec 11, 2015
· national
Continuity (8)
Provisional Application
62266233
· Dec 11, 2015
References Cited (229)
US 7060275B2
· Mueller et al.
· 2006
[cited by applicant]
US 7205121B2
· Palka-Hamblin et al.
· 2007
[cited by applicant]
US 7268222B1
· Harras et al.
· 2007
[cited by applicant]
US 7358231B1
· McCaffey et al.
· 2008
[cited by applicant]
US 7399469B2
· Zhang et al.
· 2008
[cited by applicant]
US 7608413B1
· Joseloff et al.
· 2009
[cited by applicant]
US 7745391B2
· Mintz et al.
· 2010
[cited by applicant]
US 7820786B2
· Thomson et al.
· 2010
[cited by applicant]
US 7842467B1
· Heidbrink et al.
· 2010
[cited by applicant]
US 7892770B2
· Cao et al.
· 2011
[cited by applicant]
US 7919467B2
· Ramakrishna et al.
· 2011
[cited by applicant]
US 7932031B2
· Lee et al.
· 2011
[cited by applicant]
US 7951546B2
· Frantz et al.
· 2011
[cited by applicant]
US 7960134B1
· Ashwell et al.
· 2011
[cited by applicant]
US 7960158B1
· Ashwell et al.
· 2011
[cited by applicant]
US 7964365B2
· Bottaro et al.
· 2011
[cited by applicant]
US 7968681B2
· Stemmer et al.
· 2011
[cited by applicant]
US 7998689B2
· Joseloff et al.
· 2011
[cited by applicant]
US 8168602B2
· DePinho et al.
· 2012
[cited by applicant]
US 8304199B2
· Bottaro et al.
· 2012
[cited by applicant]
US 8309315B2
· Cao et al.
· 2012
[cited by applicant]
US 8455623B2
· Horst et al.
· 2013
[cited by applicant]
US 8586006B2
· Hood et al.
· 2013
[cited by applicant]
US 8617831B2
· Bottaro et al.
· 2013
[cited by applicant]
US 8647629B2
· Rammensee et al.
· 2014
[cited by applicant]
US 9220755B2
· Chakraborty
· 2015
[cited by examiner]
US 9498512B2
· Rammensee et al.
· 2016
[cited by applicant]
US 9943579B2
· Weinschenk et al.
· 2018
[cited by applicant]
US 20050239700A1
· Kloetzer et al.
· 2005
[cited by applicant]
US 20070065447A1
· Tryggvason et al.
· 2007
[cited by applicant]
US 20080025981A1
· Young et al.
· 2008
[cited by applicant]
US 20090274714A1
· Singh et al.
· 2009
[cited by applicant]
US 20090275633A1
· Esteller
· 2009
[cited by applicant]
US 20110142842A1
· Olweus et al.
· 2011
[cited by applicant]
US 20120070450A1
· Ishikawa et al.
· 2012
[cited by applicant]
US 20140086943A1
· Weinschenk et al.
· 2014
[cited by applicant]
US 20140234351A1
· Bender et al.
· 2014
[cited by applicant]
US 20160168200A1
· Weinschenk et al.
· 2016
[cited by applicant]
CN 101066991A
· 2007
[cited by applicant]
CN 1621414A
· 2011
[cited by applicant]
EP 1118860A1
· 2001
[cited by applicant]
EP 1760089A1
· 2007
[cited by applicant]
EP 1760088B1
· 2008
[cited by applicant]
WO 0190197A1
· 2001
[cited by applicant]
WO 2007028574A2
· 2007
[cited by applicant]
WO 20070150077A2
· 2007
[cited by applicant]
WO 2008118017A2
· 2008
[cited by applicant]
WO 2009036246A2
· 2009
[cited by applicant]
WO 20090036246A2
· 2009
[cited by applicant]
WO 20090059804A2
· 2009
[cited by applicant]
WO WO2009138236A1
· 2009
[cited by examiner]
WO 20120178087A1
· 2012
[cited by applicant]
WO 2013177533A2
· 2013
[cited by applicant]
WO 20150018805A1
· 2015
[cited by applicant]
WO 2015188839A2
· 2015
[cited by applicant]
WO 2017089768A1
· 2017
[cited by applicant]
WO 2017096304A1
· 2017
[cited by applicant]
WO 2019075385A1
· 2019
[cited by applicant]
Search Report from GB Application No. 1521894.4 received Sep. 22, 2016.
[cited by applicant]
GENE (epub Sep. 2015); vol. 575, pp. 438-451, “Analysis of the Fam181 gene family . . . ” Marks et al.
[cited by applicant]
International Search Report for PCT/EP2016/079737, mailed May 3, 2017.
[cited by applicant]
Walter et al., “Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival”, Nature Medicine., vol. 18, No. 8, Aug. 2012 (Aug. 2012), pp. 1254-1265, …
[cited by applicant]
Weinschenk, et al., “Integrated functional genomics approach for the design of patient-individual antitumor vaccines.” Cancer Research, American Association for Cancer Research, US. vol. 62, No. 20, Oct. 15, 2002 (Oct. …
[cited by applicant]
Hinrichs et al., Nature Biotechnology vol. 31 p. 999 (2013).
[cited by applicant]
Baruch et al. (Cancer vol. 123 p. 2154 (2017)).
[cited by applicant]
Li et al., “Identification of a new HLA-A 0201-restricted CD8+ T cell epitope from hepatocellular carcinoma-associated antigen HCA587,” Clinical and Experimental Immunology, (2005), vol. 140: 310-319.
[cited by applicant]
Inoue, H., et al. “Human esophageal carcinomas frequently express the tumor-rejection antigens of MAGE genes” International Journal of Cancer, vol. 63, No. 4, pp. 523-526, Nov. 1995.
[cited by applicant]
Janakiram, Naveena B., et al. “Adoptive Transfer of Regulatory T Cells Promotes Intestinal Tumorigenesis and is Associated With Decreased NK Cells and IL-22 Binding Protein” Molecular Carcinogenesis, vol. 54, No. 10, pp…
[cited by applicant]
Jarmalavicius, Saulius et al., “High Immunogenicity of the Human Leukocyte Antigen Peptidomes of Melanoma Tumor Cells”, The Journal of Biological Chemistry, Sep. 28, 2012, pp. 33401-33411, vol. 287, No. 40.
[cited by applicant]
Jones, Robert T., et al. “Pharmacogenomics: Biomarker-Directed Therapy for Bladder Cancer” Urol. Clim North America, vol. 43, No. 1, pp. 77-86, Feb. 2016.
[cited by applicant]
Juncher, Henning, et al. “The Solubility of Oral Preparations of Penicilin V” Antibiotic Med. Clin. Ther. Vol. 4, No. 9, pp. 497-507, Sep. 1957.
[cited by applicant]
Kalos, Michael, et al. “T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia” Science Translational Medicine, vol. 3, No. 95, Aug. 2011.
[cited by applicant]
Kaufman, Howard L., et al. “Combination Chemotherapy and ALVAC-CEA/B7.1Vaccine in Patients with Metastatic Colorectal Cancer” Clinical Cancer Research, vol. 14, No. 15, pp. 4843-4849, Aug. 1, 2008.
[cited by applicant]
Khong, Hung T., et al. “Natural selection of tumor variants in the generation of “tumor escape” phenotypes” Natural Immunology, vol. 3, No. 11, pp. 999-1005, Nov. 2002.
[cited by applicant]
Kimura, Hitoshi, et al. “Prognostic significance of EpCAM expression in human esophageal cancer” International Journal of Oncology, vol. 30, No. 1, pp. 171-179, Jan. 2007.
[cited by applicant]
Knollman, Hayley, et al. “Muscle-invasive urothelial bladder cancer: an update on systemic therapy” Ther Adv Urol. vol. 7, No. 6, pp. 312-330, Dec. 2015.
[cited by applicant]
Koido, Shigeo, et al. “Immunotherapy for colorectal cancer” World of Gastroenterology, vol. 19, No. 46, pp. 8531-8542, Dec. 2013.
[cited by applicant]
Kono, Koji, et al. “ Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer” Cancer Science, vol. 100, No. …
[cited by applicant]
Krackhardt, Angela M., et al. “Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX” Blood, vol. 100, No. 6, pp. 2123-2131, Sep. 2002.
[cited by applicant]
Kronenberger, Konrad, et al. “A Polyvalent Cellular Vaccine Induces T-cell Responses Against Specific Self-antigens Overexpressed in Chronic Lymphocytic B-cell Leukemia” Journal of Immunotherapy, vol. 31, Issue 8, pp. 7…
[cited by applicant]
Lee, Wei-Chen, et al. , “Vaccination of Advanced Hepatocellular Carcinoma Patients with Tumor Lysate-Pulsed Dendritic Cells: A Clinical Trial” Journal of Immunotherapy, vol. 28, No. 5, pp. 496-504, Sep./Oct. 2005.
[cited by applicant]
Liang, Zhen, et al. “[The expression of 11 cancer/testis (CT) antigen genes in esophageal carcinoma]” Chinese Journal of Oncology, vol. 27, No. 9, pp. 534-7, Sep. 2005 (translation of abstract only).
[cited by applicant]
Liu, Zuqiang, et al. “Potent Tumor-Specific Protection Ignited by Adoptively Transferred CD4+ T Cells” Journal of Immunology, vol. 181, No. 6, pp. 4363-4370, Sep. 2008.
[cited by applicant]
Llovet, Josep M., et al., “Sorafenib in Advanced Hepatocellular Carcinoma” New England Journal of Medicine, vol. 359, pp. 378-390, Dec. 4, 2008.
[cited by applicant]
Lollini, Pier-Luigi, et al. “Cancer immunoprevention: tracking down persistent tumor antigens” Trends in Immunology, vol. 24, No. 2, pp. 62-66, Feb. 2003.
[cited by applicant]
Lollini, P-L., et al. “New target antigens for cancer immunoprevention” Current Cancer Drug targets, vol. 5, No. 3, pp. 221-228, May 2005.
[cited by applicant]
Maerten, Angela, et al. “Therapeutic vaccination against metastatic renal cell carcinoma by autologous dendritic cells: preclinical results and outcome of a first clinical phase I/II trial” Cancer Immunology, Immunother…
[cited by applicant]
Mantia-Smaldone, Gina M., et al. “Immunotherapy in ovarian cancer” Human Vaccin Innumotherapy, vol. 8, No. 9, pp. 1179-1191, Sep. 2012.
[cited by applicant]
Massari, F., et al. “PD-1 blockade therapy in renal cell carcinoma: Current studies and future promises” Cancer Treatment Reviews, vol. 41, No. 2, pp. 114-121, Feb. 2015.
[cited by applicant]
Matsueda, Satoko, et al. “Immunotherapy in gastric cancer” World Journal of Gastroenterology, vol. 20, Issue 7, pp. 1657-1666, Feb. 21, 2014.
[cited by applicant]
Maus, Marcela V., et al. “Antibody-modified T cells: CARs take the front seat for hematologic malignancies” Blood, vol. 123, No. 17, pp. 2625-2635, Apr. 2014.
[cited by applicant]
Mayr, Christine, et al. “Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes” Blood, vol. 105, No. 4, pp. 1566-1…
[cited by applicant]
Mayr, Christine, et al. “MDM2 is recognized as a tumor-associated antigen in chronic lymphocytic leukemia by CD8+ autologous T lymphocytes” Experimental Hematology, vol. 31, No. 1, pp. 44-53, Jan. 2006.
[cited by applicant]
Menoret, Antoine, et al. “Association of Peptides with Heat Shock Protein gp96 Occurs in Vivo and Not after Cell Lysis” Biochemical and Biophysical Research Communications, vol. 262, No. 3, pp. 813-818, Sep. 1999.
[cited by applicant]
Miyagi, Yoshiaki, et al. “Induction of Cellular Immune Responses to Tumor Cells and Peptides in Colorectal Cancer Patients by Vaccination with SART3 Peptides1” Clinical Cancer Research, vol. 7, pp. 3950-3962, Dec. 2001.
[cited by applicant]
Molina, Julian R., et al. “Non-Small Cell Lung Cancer: Epidemiology, Risk Factors, Treatment, and Survivorship” Mayo Clinic Proceedings, vol. 83, No. 5m pp. 584-594, May 2008.
[cited by applicant]
Morozowich, W., et al. “Relationship between in Vitro Dissolution Rates, Solubilities, and LT50s in Mice of Some Salts of Benzphetamine and Etryptamine” Journal of Pharmaceutical Science, vol. 51, No. 10, pp. 993-995, 1…
[cited by applicant]
Mortara, Lorenzo, et al. “CIITA-Induced MHC Class II Expression in Mammary Adenocarcinoma Leads to a Th1Polarization of the Tumor Microenvironment, Tumor Rejection, and Specific Antitumor Memory” Clinical Cancer Researc…
[cited by applicant]
Moulton, Hong M., et al. “Active Specific Immunotherapy with a -Human Chorionic Gonadotropin Peptide Vaccine in Patients with Metastatic Colorectal Cancer: Antibody Response is Associated with Improved Survival1” Clinic…
[cited by applicant]
Mueller, Martin R., et al. “Induction of chronic lymphocytic leukemia (CLL)-specific CD4- and CD8-mediated T-cell responses using RNA-transfected dendritic cells” Blood, vol. 103, No. 5, pp. 1763-1769, Mar. 2004.
[cited by applicant]
Mumberg, Dominik, et al. “CD41 T cells eliminate MHC class Il-negative cancer cells in vivo by indirect effects of IFN-y” Immunology, vol. 96, pp. 8633-8638, Jul. 1999.
[cited by applicant]
Neeley, Yilin C., et al. “Partially Circumventing Peripheral Tolerance for Oncogene-Specific Prostate Cancer Immunotherapy” The Prostate, vol. 68, No. 7, pp. 715-727, May 2008.
[cited by applicant]
O'Connor, Colleen M., et al. “Adoptive T-cell therapy improves treatment of canine non-Hodgkin lymphoma post chemotherapy” Scientific Reports, vol. 2, No. 249, pp. 1-12, 2012.
[cited by applicant]
Ohigashi, Yuichiro, et al. “Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer” Clinical Cancer Research, vol. 11, No. 8, pp. 2947-2953, Apr. 2005.
[cited by applicant]
Okuno, Kiyotaka, et al. “Phase I clinical trial of a novel peptide vaccine in combination with UFT/LV for metastatic colorectal cancer” Experimental and Therapeutic Medicine, vol. 2, pp. 73-79, Jan. 2011.
[cited by applicant]
Palma, M., et al. “Development of a dendritic cell-based vaccine for chronic lymphocytic leukemia” Cancer Immunol. mmunother. vol. 57, No. 11, pp. 1705-1710, Nov. 2008.
[cited by applicant]
Palmer, Daniel H., et al., “A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma”, Hepatology, vol. 49, pp. 124-132, Jan. 2009.
[cited by applicant]
Palomba, M. Lia. “Active immunotherapy: current state of the art in vaccine approaches for NHL” Current Oncology Reports, vol. 14, No. 5, pp. 433-440, Oct. 2012.
[cited by applicant]
Parikh, Sameer A., et al. “Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia” Blood, vol. 118, No. 8, pp. 2062, 2068, Aug. 2011.
[cited by applicant]
Phan, Giao Q., et al. “Adoptive cell transfer for patients with metastatic melanoma: the potential and promise of cancer immunotherapy” Cancer Control, vol. 20, No. 4, pp. 289-297, Oct. 2013.
[cited by applicant]
Porter, David L., et al. “Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia” New England Journal of Medicine, vol. 365, No. 8, pp. 725-733, Aug. 2011.
[cited by applicant]
Prato, Sandro, et al. “Rapid Deletion and Inactivation of CTLs upon Recognition of a Number of Target Cells over a Critical Threshold” Journal of Immunology, vol. 191, No. 7, pp. 3534-3544, Oct. 2013.
[cited by applicant]
Pritchard, Antonia L. et al., “Exploration of Peptides Bound to MHC Class | Molecules in Melanoma”, Pigment Cell Melanoma Research, vol. 28, No. 3, May 2015 (Abstract Only).
[cited by applicant]
Quillen, V., et al. “Expression of MAGE genes in esophageal squamous-cell carcinoma” Anticancer Research, vol. 17, No. 1A, pp. 387-391, Jan. 1997 (abstract Only).
[cited by applicant]
Quinn, David I., et al. “Immunotherapy for castration-resistant prostate cancer: Progress and new paradigms” Urologic Oncology, vol. 33, No. 5, pp. 245-260, May 2015.
[cited by applicant]
Ramanathan, Sheela, et al.“Antigen-nonspecific activation of CD8+ T lymphocytes by cytokines: relevance to Immunity, autoimmunity, and cancer” Arch. Immunol. Ther. Exp. (Warsz), vol. 56, No. 5, pp. 311-323, Sep. 2008.
[cited by applicant]
Reinisch et al., “Prospective Pilot Study of Recombinant Granulocyte-Macrophage Colony-Stimulating Factor and Interferon-y in Patients With Inoperable Hepatocellular Carcinoma” Journal of Immunotherapy, vol. 25, No. 6, …
[cited by applicant]
Reinmuth, Niels, et al. “[Non-small cell lung cancer: news from immunotherapy]” Dtsch Med Wochenschr, vol. 140, No. 5, pp. 329-333, Mar. 2015.
[cited by applicant]
Restifo, Nicholas P., et al. “Loss of Functional Beta2-Microglobulin in Metastatic Melanomas From Five Patients Receiving Immunotherapy” Journal National Cancer Institute, vol. 88, No. 2, pp. 100-108, Jan. 1996.
[cited by applicant]
Richards, S., et al. “Chemotherapeutic Options in Chronic Lymphocytic Leukemia: a Meta-analysis of the Randomized Trials” J Natl. Cancer Inst vol. 91, pp. 861-868, May 1999.
[cited by applicant]
Robak, Tadeusz, et al. “Anti-CD37 antibodies for chronic lymphocytic leukemia” Expert Opinion on Biological Therapy, vol. 14, No. 5, pp. 651-661, Feb. 2014.
[cited by applicant]
Rock, K.L., et al. “Presentation of exogenous antigen with class I major histocompatibility complex molecules” Science, vol. 249, No. 4971, pp. 918-921, Aug. 1990.
[cited by applicant]
Rosenberg, S.A., “Gene transfer into humans-immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction” New England Journal of Medicine, vol. 323, No.…
[cited by applicant]
Rosenberg, Steven A., et al. “Adoptive cell transfer: a clinical path to effective cancer immunotherapy” Nat. Rev. Cancer, vol. 8, No. 4, pp. 299-308, Apr. 2008.
[cited by applicant]
Rouanne, Mathieu, et al. “Novel therapeutic targets in advanced urothelial carcinoma” Critical Review Oncol Hematology, vol. 98, pp. 106-115, Feb. 2016.
[cited by applicant]
Rudolph, Despina, et al. “Potent costimulation of human CD8 T cells by anti-4-1BB and anti-CD28 on synthetic artificial antigen presenting cells” Cancer Immunol. Immunotherapy, vol. 57, No. 2, pp. 175-183, Feb. 2008.
[cited by applicant]
Saesmaa, Tarja, et al. “Dissolution studies on ampicillin embonate and amoxycillin embonate” Journal of Pharmaceutical & Biomedical Analysis, vol. 8, No. 1, pp. 61-65, 1990.
[cited by applicant]
Salman, Bulent, et al. “Vaccine therapy for pancreatic cancer” Oncoimmunology, vol. 2, No. 12, article e26662, Dec. 2013.
[cited by applicant]
Sangro, Bruno, et al., “Phase I Trial of Intratumoral Injection of an Adenovirus Encoding Interleukin-12 for Advanced Digestive Tumors”, Journal of Clinical Oncology, vol. 22, No. 8, pp. 1389-1397, Apr. 15, 2004.
[cited by applicant]
Schmidt, Susanne M., et al. “Induction of adipophilin-specific cytotoxic T lymphocytes using a novel HLA-A2-binding peptide that mediates tumor cell lysis” Cancer Research, vol. 64, No. 3, pp. 1164-1170, Feb. 2004.
[cited by applicant]
Schultze, J. L., et al. “A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2” British Journal of Haematol…
[cited by applicant]
Shi, M., “Autologous cytokine-induced killer cell therapy in clinical trial phase I is safe in patients with primary hepatocellular carcinoma”, World Journal of Gastroenterology, vol. 10, No. 8, pp. 1146-1151, Apr. 15, …
[cited by applicant]
Siegel, Sandra, et al. “Induction of cytotoxic T-cell responses against the oncofetal antigen-immature laminin receptor for the treatment of hematologic malignancies” Blood, vol. 102, No. 13, pp. 4416-4423, Dec. 2003.
[cited by applicant]
Singh-Jasuja, Harpreet et al. “!The Tuebingen approach: identification, selection, and validation of tumor-associated HLA peptides for cancer therapy” Cancer Immunology, Immunotherapy, vol. 53, pp. 187-185, Jan. 2004.
[cited by applicant]
Slingluff, Craig L., Jr., et al. Melanomas with concordant loss of multiple melanocyctic differentiation proteins: Immune escape that may be overcome by targeting unique or undefined antigens Cancer Immunology Immunothe…
[cited by applicant]
Spaner, David E., et al. “A phase I/II trial of oxidized autologous tumor vaccines during the “watch and wait” phase of chronic lymphocytic leukemia” Cancer Immunol. Immunother. vol. 54, No. 7, pp. 635-646, Jul. 2005.
[cited by applicant]
Srivastava, Neeharika, et al. “Update on benefit of immunotherapy and targeted therapy in melanoma: the changing landscape” Cancer Manag Res. vol. 6, pp. 279-289, Jun. 2014.
[cited by applicant]
Stevanovic, Sanja, et al. “Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells” Journal of Clinical Oncology, vol. 33, No. 14, pp. 1543-1550, M…
[cited by applicant]
Stevens, James, et al. “Peptide length preferences for rat and mouse MHC class I molecules using random peptide libraries” European Journal of immunology, vol. 28, No. 4, pp. 1272-1279, Mar. 2013.
[cited by applicant]
Stintzing, Sebastian. “Management of colorectal cancer” F1000Prime Reports, vol. 6, No. 108, Nov. 2014 (12 pages).
[cited by applicant]
Su, Zhen, et al. “Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells” Cancer Research, vol. 63, No. 9, pp. 2127-2133, May 2003.
[cited by applicant]
Takayama, “Distribution and therapeutic effect of intraarterially transferred tumor—infiltrating lymphocytes in hepatic malignancies”, A Preliminary Report, Cancer, vol. 68 (11), Mar. 19, 1991, pp. 2391-2396.
[cited by applicant]
Takayama, Tadatoshi, et al., “Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial”, The Lancet, vol. 356, pp. 802-807, Sep. 2, 2000.
[cited by applicant]
Tanaka, F., et al. “High frequency of the expression of the MAGE gene family in human esophageal carcinoma” International Journal of Oncology, vol. 10, No. 6, pp. 1113-1117, Jun. 1997.
[cited by applicant]
Thakkar, Jigisha P., et al. “Epidemiologic and Molecular Prognostic Review of Glioblastoma” Cancer Epidemiol. Biomarkers Prev. vol. 23, No. 10, pp. 1985-1996, Oct. 2014.
[cited by applicant]
Toh, Uhi, et al. “Locoregional adoptive immunotherapy resulted in regression in distant metastases of a recurrent esophageal cancer” International Journal of Clinical Oncology, vol. 7, No. 6, pp. 372-375, Dec. 2002.
[cited by applicant]
Toh, Uhi, et al. “Locoregional cellular immunotherapy for patients with advanced esophageal cancer” Clinical Cancer Research, vol. 6, No. 12, pp. 4663-4673, Dec. 2000.
[cited by applicant]
Toomey, Paul G., et al. “Immunotherapy for gastrointestinal malignancies” Cancer Control. vol. 20, No. 1, pp. 32-42, Jan. 2013.
[cited by applicant]
Tran, Eric, et al. “Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer” Science, vol. 344, No. 6184, pp. 641-645, May 2014.
[cited by applicant]
Vici, Patrizia, et al. “Immunologic treatments for precancerous lesions and uterine cervical cancer” Journal Experimental Clinical Cancer Research, vol. 33, No. 1, Mar. 2014.
[cited by applicant]
Von Rundstedt, Friedrich-Carl, et al. “Bacille-Calmette-Guerin non-responders: how to manage” Transl. Androl. Urol. vol. 4, No. 3, pp. 244-253, Jun. 2015.
[cited by applicant]
Vonderheide, Robert H., et al. “Agonistic CD40 antibodies and cancer therapy” Clinical Cancer Research, vol. 19, No. 5, pp. 1035-1043, Mar. 2013.
[cited by applicant]
Wierda, William G., et al. “Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study” Blood, vol. 118, No. 19, pp. 5126-5129, Nov. 20…
[cited by applicant]
Wilhelm et at, “BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis”. Cancer Res. vol. 64, Oct. 1,…
[cited by applicant]
Wilson, Peter M., et al. “Standing the test of time: targeting thymidylate biosynthesis in cancer therapy” Nature, vol. 11, pp. 282-298, May 2014.
[cited by applicant]
Wittig, B., et al. “Therapeutic vaccination against metastatic carcinoma by expression-modulated and Immunomodified autologous tumor cells: a first clinical phase I/II trial” Human Gene Therapy, vol. 12, No. 3, pp. 267-…
[cited by applicant]
York, Ian A., et al. “The Cytosolic Endopeptidase, Thimet Oligopeptidae, Destroys Antigenic Peptides and Limits the Extent of MHC Class | Antigen Presentation” Immunity, vol. 18, No. 3, pp. 429-440, Mar. 2003.
[cited by applicant]
Accardi, Luisa, et al. “In vivo antitumor effect of an intracellular single-chain antibody fragment against the E7 oncoprotein of human papillomavirus 16” International Journal of Cancer, vol. 134, No. 11, pp. 2742-2747…
[cited by applicant]
Albrecht, Jana, et al. “IL-21-treated naive CD45RA+ CD8+ T cells represent a reliable source for producing leukemia-reactive cytotoxic T lymphocytes with high proliferative potential and early differentiation phenotype”…
[cited by applicant]
Ampie, Leonel, et al. “Immunotherapeutic advancements for glioblastoma” Frontiers in Oncology, vol. 5, Article 12, Jan. 2015.
[cited by applicant]
Arceci, Robert J. “The potential for antitumor vaccination in acute myelogenous leukemia” Journal of Molecular Medicine, vol. 76, pp. 80-93, 1998.
[cited by applicant]
Avigan, David, et al. “Fusion Cell Vaccination of Patients with Metastatic Breast and Renal Cancer Induces Immunological and Clinical Responses” Clinical Cancer Research, vol. 10, pp. 4699-4708, Jul. 15, 2004.
[cited by applicant]
Beatty, Gregory L., et al. “IFN-g-Dependent Inhibition of Tumor Angiogenesis by Tumor-Infiltrating CD41 T Cells Requires Tumor Responsiveness to IFN-y1” Journal of Immunology, vol. 166, No. 4, pp. 2276-2282, Feb. 15, 20…
[cited by applicant]
Bodey, Bela, et al. “Failure of Cancer Vaccines: The Significant Limitations of the Approach to Immunotherapy” Anticancer Research, vol. 20, No. 4, pp. 2665-2676, Jul.-Aug. 2000.
[cited by applicant]
Braumueller, Heidi, et al. “T-helper-1-cell cytokines drive cancer into senescence” Nature, vol. 494, pp. 361-365, Feb. 2013.
[cited by applicant]
Bray, Freddie, et al. “Global estimates of cancer prevalence for 27 sites in the adult population in 2008” International Journal of Cancer, vol. 132, pp. 1133-1145, 2013.
[cited by applicant]
Brossart, Peter and Bevan, Michael J. “Presentation of Exogenous Protein Antigens on Major Histocompatability Complex Class | Molecules by Dendritic Cells: Pathway of Presentation and Regulation by Cytokines” Blood, vol…
[cited by applicant]
Bujas, T., et al. “MAGE-A3/4 and NY-ESO-1 antigens expression in metastatic esophageal squamous cell carcinoma” European Journal Histochem. vol. 55, No. 1, Mar. 2011.
[cited by applicant]
Butterfield, Lisa H., et al., “A Phase I/II Trial Testing Immunization of Hepatocellular Carcinoma Patients with Dendritic Cells Pulsed with Four a-Fetoprotein Peptides”, Clinical Cancer Research, vol. 12, No. 9, pp. 28…
[cited by applicant]
Butterfield, Lisa H., et al., “Determinant Spreading Associated with Clinical Response in Dendritic Cell-based Immunotherapy for Malignant Melanoma”, Clinical Cancer Research, vol. 9, pp. 998-1008, Mar. 2003.
[cited by applicant]
Carballido, Estrella, et al. “Immunomodulatory Drugs and Active Immunotherapy for Chronic Lymphocytic eukemia” Cancer Control, vol. 19, Issue 1, pp. 4-76, Jan. 2012.
[cited by applicant]
Chang, A. et al. “Clinical observations on adoptive immunotherapy with vaccine-primed T-lymphocytes secondarily sensitized to tumor in vitro” Cancer Research, vol. 53, No. 5, pp. 1043-1050, Mar. 1993.
[cited by applicant]
Chang, Yong S., et al., “Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models”, Cancer Chemother. Pharmacol. vol. 59, No. 5, pp. 561-574, Apr.…
[cited by applicant]
Chapiro, Julius, et al., “Combination of intra-arterial therapies and sorafenib: Is there a clinical benefit?” Radiol. Med. vol. 119, pp. 476-482, Jul. 2014.
[cited by applicant]
Chen, Liya, et al. “Critical role of endoplasmic reticulum aminopeptidase 1 in determining the length and sequence of peptides bound and presented by HLA-B27” Arthritis Rheumatol., vol. 66, No. 2, pp. 284-294, Feb. 2014.
[cited by applicant]
Chen, Ting, et al. “Identification of trypsin-inhibitory site and structure determination of human SPINK2 serine proteinase inhibitor” Proteins, vol. 77, No. 1, pp. 209-219, Oct. 2009.
[cited by applicant]
Coosemans, An, et al. “Wilms' Tumor Gene 1 (WT1)—loaded dendritic cell immunotherapy in patients with uterine tumors: a phase I/II clinical trial” Anticancer Research, vol. 33, No. 12, pp. 5495-5500, Dec. 2013.
[cited by applicant]
Counter, C.M., “Telomerase activity in normal leukocytes and in hematologic malignancies” Blood, vol. 85, No. 9, pp. 2315-2320, May 1995.
[cited by applicant]
Cunha, Fernanda, et al. “Intracellular Peptides as Natural Regulators of Cell Signaling” Journal of Biological Chemistry, vol. 283, No. 36, pp. 24448-59, Sep. 2008.
[cited by applicant]
Dengjel, Jom, et al. “Unexpected Abundance of HLA Class II Presented Peptides in Primary Renal Cell Carcinomas” Clinical Cancer Research, vol. 12, No. 14, Jul. 15, 2006.
[cited by applicant]
Di Renzo, M.F., et al. “Expression of the Met/HGF receptor in normal and neoplastic human tissues” Oncogenetics, vol. 6, No. 11, pp. 1997-2003, Nov. 1991.
[cited by applicant]
Di Schiavi, et al. “UMODL 1/Olfactorin is an extracellular membrane-bound molecule with a restricted spatial expression in olfactory and vomeronasal neurons” European Journal of Neuroscience, vol. 21, No. 12, pp. 3291-3…
[cited by applicant]
Distler, Eva, et al. “Patient-individualized CD8+ cytolytic T-cell therapy effectively combats minimal residual leukemia in immunodeficient mice” International Journal of Cancer, vol. 138, No. 5, Mar. 2016.
[cited by applicant]
Drexler, H. G., et al. “Terminal deoxynucleotidyl transferase (TdT) expression in acute myeloid leukemia” Leukemia, vol. 7, No. 8, pp. 1142-1150, Aug. 1993.
[cited by applicant]
Economopoulou, Panagiota, et al. “The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications” Annals of Translational Medicine, vol. 4, No. 9, Arti…
[cited by applicant]
Emens, Leisha A. “Breast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockade” Expert Review Anticancer Therapy, vol. 12, No. 12, pp. 1597-1611, Dec. 2012.
[cited by applicant]
Estey, Elihu H. “Acute myeloid leukemia: 2014 update on risk-stratification and management” American Journal of Hematology, vol. 89, No. 11, pp. 1063-1081, Nov. 2014.
[cited by applicant]
Farahat, N., et al. “Differential TdT expression in acute leukemia by flow cytometry: a quantitative study” Leukemia., vol. 9, No. 4, pp. 583-587, Apr. 1995.
[cited by applicant]
Ferlay, J., et al. “Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012” European Journal of Cancer, vol. 49, pp. 1374-1403, Apr. 2013.
[cited by applicant]
Fuge, Oliver, et al. “Immunotherapy for bladder cancer” Research and Reports in Urology, vol. 7, pp. 65-79, May 2015.
[cited by applicant]
Gandhi, Ankit V., et al. “Differential expression of cytochrome P450 omega-hydroxylase isoforms and their association with clinicopathological features in pancreatic ductal adenocarcinoma” Annals Surgical Oncology, vol.…
[cited by applicant]
Giannopolous, K., et al. “Peptide vaccination elicits leukemia-associated antigen-specific cytotoxic CD8+ T-cell responses in patients with chronic lymphocytic leukemia” Leukemia, vol. 24, No. 4, pp. 798-805, Apr. 2010.
[cited by applicant]
Giannopoulos, K., et al. “Expression of RHAMM/CD168 and other tumor-associated antigens in patients with B-cell chronic lymphocytic leukemia” International Journal of Oncology, vol. 29, No. 1, pp. 95-103, Jul. 2006.
[cited by applicant]
Gnjatic, Sacha, et al. “Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses” PNAS, vol. 100, No. 15, pp. 8862-8867. Jul. 22, 2003.
[cited by applicant]
Goede, Valentin, et al. “Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions” New England Journal of Medicine, vol. 370, No. 12, pp. 1101-1110, Mar. 2014.
[cited by applicant]
Granziero, L., et al. “Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia” Blood, vol. 97, No. 9, pp. 27777-83, May 2001.
[cited by applicant]
Grivas, Petros D., et al. “The biological complexity of urothelial carcinoma: Insights into carcinogenesis, targets and biomarkers of response to therapeutic approaches” Semin Cancer Biol. vol. 35, pp. 125-132, Dec. 201…
[cited by applicant]
Gunawardana, Chaminda, et al. “South Asian chronic lymphocytic leukemia patients have more rapid disease progression in comparison to White patients.” British journal of haematology 142, No. 4 (2008): 606-609.
[cited by applicant]
Gura, Trisha. “Systems for Identifying New Drugs are Often Faulty” Science, vol. 278, No. 5340, pp. 1041-1042, Nov. 1997.
[cited by applicant]
Hallek, M., et al. “Immunochemotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) versus fludarabine and cyclophosphamide (FC) improves response rates and progression-free survival (PFS) of prev…
[cited by applicant]
Harig, S., et al. “Induction of cytotoxic T-cell responses against immunoglobulin V region-derived peptides modified at human leukocyte antigen-A2 binding residues” Blood, vol. 98, No. 10, pp. 29999-3005, Nov. 2001.
[cited by applicant]
Hilpert, Kai, et al. “Peptide arrays on cellulose support: SPOT sunthesis, a time and cost efficient method for synthesis of large numbers of peptides in a parallel and addressable fashion” Nat. Protoc. vol. 2, No. 6, p…
[cited by applicant]
Holtl, Lorenz, et al. “Immunotherapy of Metastatic Renal Cell Carcinoma with Tumor Lysate-pulsed Autologous Dendritic Cells1” Clinical Cancer Research, vol. 8, pp. 3369-3376, Nov. 2002.
[cited by applicant]
Horig, Heidi, et al. “Phase I clinical trial of a recombinant canarypoxvirus (ALVAC) vaccine expressing human carcinoembryonic antigen and the B7.1 co-stimulatory molecule” Cancer Immunology, Immunotherapy, vol. 49, No.…
[cited by applicant]
Hung, Chien-Fu, et al. “Antigen-specific immunotherapy of cervical and ovarian cancer” Immunological Review, vol. 222, pp. 43-69, Apr. 2008.
[cited by applicant]
Hus, Iwona, et al. “Immunotherapy with irradiated autologous leukemic cells in patients with B-CLL in early stages” Oncology Rep. vol. 20, No. 2, pp. 443-451, Aug. 2008.
[cited by applicant]
Hwang. Melissa L., et al. “Cognate memory CD4+ T cells generated with dendritic cell priming influence the expansion, trafficking, and differentiation of secondary CD8+ T cells and enhance tumor control” Journal of Immu…
[cited by applicant]
Kessler J H et al. “Efficient Identification of Novel HLA-A 0201-presented Cytotoxic T Lymphocyte Epitopes in the Widely Expressed Tumor Antigen PRAME by Proteasome-mediated Digestion Analysis,” The Journal of Experimen…
[cited by applicant]
Kiessling, et al., “Identification of an HLA-A 0201-restricted T-cell epitope derived from the prostate cancer-associated protein prostein,” British Journal of Cancer vol. 90, pp. 1034-1040 (2004).
[cited by applicant]
Xing et al., “Identification of new cytotoxic T-lymphocyte epitopes from cancer testis antigen HCA587,” Biochemical and Biophysical Research Communications, vol. 372, No. 2, pp. 331 to 335. Jul. 25, 2008—abstract provid…
[cited by applicant]