Granted Patent
B2
US 12,285,438 · App. 17/701,535 · Granted Apr 29, 2025
Enhanced immune cells using dual shRNA and composition including the same
Inventors:
Chan Hyuk Kim (Daejeon, KR); Young-Ho Lee (Daejeon, KR); Yujean Lee (Daejeon, KR); HyeongJi Lee (Daejeon, KR); Sang Hoon Lee (Daejeon, KR)
A61K31/7088A61K38/177A61K38/1774A61K39/3955A61K39/4611A61K39/4631A61K39/4636A61K39/464412A61P35/00C07K14/4702C07K14/7051C07K14/70521C07K14/70578C07K16/2803C12N5/0636C12N5/0637C12N5/0646C12N15/1138A61K2039/505A61K2239/31A61K2239/48C07K2317/53C07K2317/622C07K2319/02C07K2319/03C07K2319/30C07K2319/33C07K2319/715C12N2310/122C12N2310/14C12N2310/531C12N2320/31C12N2320/32C12N2510/00
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present disclosure is broadly concerned with the field of cancer immunotherapy. For example, the present invention generally relates to an immune cell comprising a genetically engineered antigen receptor that specifically binds to a target antigen and a genetic disruption agent that reduces or is capable of reducing the expression in the immune cell of a gene that weakens the function of the immune cell.
Claims (12)
1. A method of treating cancer, comprising administering a human-derived T cell to a human subject having cancer, said human-derived T cell comprising (i) a first nucleotide sequence encoding a first short hairpin RNA (shRNA) that inhibits expression of Programmed Cell Death 1 (PD-1) and a second shRNA that inhibits expression of T cell immunoreceptor with Ig and ITIM domains (TIGIT), and (ii) a second nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular antigen recognition domain that binds a target antigen associated with the cancer, a transmembrane domain, and an intracellular signal transduction domain comprising a CD3 intracellular domain and a 4-1BB costimulatory molecule, wherein expression of the first shRNA is regulated by a first promoter and expression of the second shRNA is regulated by a second promoter, wherein the target antigen is CD19 and wherein the cancer is a CD19 positive cancer.
2. The method of claim 1 , wherein the target antigen is a cancer antigen whose expression is increased in or on the surface of a cancer cell, a cancer tissue, and/or a tumor microenvironment.
3. The method of claim 1 , wherein the first nucleotide sequence is present on a vector.
4. The method of claim 1 , wherein the first nucleotide sequence and the second nucleotide sequence are present on a single vector.
5. The method of claim 1 , wherein the cancer is a hematological malignancy.
6. The method of claim 5 , wherein the hematological malignancy is a B cell tumor.
7. The method of claim 5 , wherein the hematological malignancy is a leukemia.
8. The method of claim 5 , wherein the hematological malignancy is a myeloma.
9. The method of claim 1 , wherein the cancer is a Programmed Cell Death Ligand 1 (PD-L1) positive cancer.
10. The method of claim 1 , wherein the first short hairpin RNA is selected by electroporating the first short hairpin RNA into CD3/CD28-stimulated cells and measuring reduced PD-1 expression.
11. The method of claim 1 , wherein the second short hairpin RNA is selected by electroporating the first short hairpin RNA into CD3/CD28-stimulated cells and measuring reduced TIGIT expression.
12. The method of claim 1 , wherein the human derived T cell is administered intravenously.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 21, 2022
From: KIM, CHAN HYUK; LEE, YOUNG-HO; LEE, YUJEAN
To: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY
Reel/Frame 060582/0791 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 21, 2022
From: LEE, HYEONGJI; LEE, SANG HOON
To: CUROCELL INC.
Reel/Frame 060583/0075 →
Priority Claims (1)
KR 10-2018-0004238
· Jan 12, 2018
· national
Continuity (2)
Continuation
16958649
References Cited (102)
US 4690915A
· Rosenberg
· 1987
[cited by applicant]
US 5858358A
· June et al.
· 1999
[cited by applicant]
US 5883223A
· Gray
· 1999
[cited by applicant]
US 6352694B1
· June et al.
· 2002
[cited by applicant]
US 6534055B1
· June et al.
· 2003
[cited by applicant]
US 6692964B1
· June et al.
· 2004
[cited by applicant]
US 6797514B2
· Berenson et al.
· 2004
[cited by applicant]
US 6867041B2
· Berenson et al.
· 2005
[cited by applicant]
US 6887466B2
· June et al.
· 2005
[cited by applicant]
US 6905680B2
· June et al.
· 2005
[cited by applicant]
US 6905681B1
· June et al.
· 2005
[cited by applicant]
US 6905874B2
· Berenson et al.
· 2005
[cited by applicant]
US 7067318B2
· June et al.
· 2006
[cited by applicant]
US 7144575B2
· June et al.
· 2006
[cited by applicant]
US 7172869B2
· June et al.
· 2007
[cited by applicant]
US 7175843B2
· June et al.
· 2007
[cited by applicant]
US 7232566B2
· June et al.
· 2007
[cited by applicant]
US 9169483B2
· Davidson et al.
· 2015
[cited by applicant]
US 9181544B2
· Davidson et al.
· 2015
[cited by applicant]
US 20080293142A1
· Liu et al.
· 2008
[cited by applicant]
US 20200399655A1
· Slepushkin et al.
· 2020
[cited by applicant]
US 20210260119A1
· Kim et al.
· 2021
[cited by applicant]
CN 106967681A
· 2017
[cited by applicant]
JP 2016526883A
· 2016
[cited by applicant]
JP 2017500869A
· 2017
[cited by applicant]
JP 2017513818A
· 2017
[cited by applicant]
RU 2015139874A
· 2017
[cited by applicant]
WO WO2014191128A1
· 2014
[cited by examiner]
WO 2015090230A1
· 2015
[cited by applicant]
WO 2015142675A2
· 2015
[cited by applicant]
WO 2015179525A1
· 2015
[cited by applicant]
WO 2016069282A1
· 2016
[cited by applicant]
WO WO2016126608A1
· 2016
[cited by examiner]
WO 2017040945A1
· 2017
[cited by applicant]
WO 2017120996A1
· 2017
[cited by applicant]
WO 2017158019A1
· 2017
[cited by applicant]
WO 2018012895A1
· 2018
[cited by applicant]
WO 2018049471A1
· 2018
[cited by applicant]
WO WO2018067991A1
· 2018
[cited by examiner]
WO 2020057486A1
· 2020
[cited by applicant]
WO 2021009701A1
· 2021
[cited by applicant]
Chauvin et al., 2015, J. Clin. Invest. vol. 125: 2046-2058.
[cited by examiner]
Lambeth, 2010, BMC molecular Biology, vol. 11: 1-15.
[cited by examiner]
Gothberg, 2016, Blood vol. 128: 917.
[cited by examiner]
Yadav, 2016, Blood, vol. 128: 2102.
[cited by examiner]
Lee, 2022, Mol. Ther. vol. 30: 579-592.
[cited by examiner]
Alberts, Molecular Biology of the Cell, 2002, Published by Garland Science, p. 121.
[cited by applicant]
Anderson et al., Lag-3, tim-3, and TIGIT co-inhibitory receptors with specialized functions in immune regulation, 2017, Immunity, 44(5), 1-34.
[cited by applicant]
Brunner et al., cytotoxic T Cells: Double-barreled shot guns, Nature Medicine, 1999, vol. 5, No. 1 p. 20.
[cited by applicant]
Cherkassky et al., 2016, “Human CART cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated Inhibition,” J. Clin. Invest., 126(8):3130-3144.
[cited by applicant]
Curran et al., 2010, “PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within BI6 melanoma tumors,” Proc. Natl. Acad. Sci. USA, 107(9):4275-4280.
[cited by applicant]
Denti et al., 2004 Molecular Therapy pp. 191-199; A New Vector, Based on the Poll I Promoter of the U 1 snRNA Gene, for the Expression of siRNAs in Mammalian Cells.
[cited by applicant]
Elbashir et al., 2001, “Elbashir SM et al., Nature, 2001, 411, 494-498,” Nature, 411(6836):494-498.
[cited by applicant]
Fewell et al., 2006, “Vector-based RNAi approaches for stable, inducible and genome-wide screens,” Drug Discov. Today, 11(21-22):975-982.
[cited by applicant]
Final Office Action issued in related U.S. Appl. No. 17/205,951 on Dec. 29, 2021 (24 pages).
[cited by applicant]
Final Office Action mailed Sep. 22, 2021 in U.S. Appl. No. 16/958,649.
[cited by applicant]
He et al., 2017, CD155T/TIGIT signaling regulates CD8 T-cell metabolism and promotes tumor progression in human gastric cancer, Cancer Res, 77(22), 6375-7388.
[cited by applicant]
Hung et al., “TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM”, Oncoimmunology, 2018, vol. 7, No. 8, 13 pages.
[cited by applicant]
Hung et al., 2018, “TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM,” Oncoimmunology, 7(8):el466769 (13 pages).
[cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/IB2020/056680 (published as WO 2021009701) mailed Oct. 29, 2020 (16 pages).
[cited by applicant]
International Search Report and Written Opinion mailed May 2, 2019 for International Patent Application No. PCT/IB2019/050194 (published as WO 2019138354), 16 pages.
[cited by applicant]
Johnston et al., 2014, “The immunoreceptor TIGIT regulates antitumor and antiviral CDS(+) T cell effector function,” Cancer Cell, 26(6):923-937.
[cited by applicant]
Josefsson et al., 2019, “TIGIT and PD-1 Mark Intratumoral T Cells With Reduced Effector Function in B-cell Non-Hodgkin Lymphoma,” Cancer Immunol Res., 7(3):355-362.
[cited by applicant]
Liddy et al., 2012, “Monoclonal TCR-redirected tumor cell killing” Nat. Med., 18(6):980-987.
[cited by applicant]
Inozume et al., Melanoma cells control antimelanoma ctl responses via interaction between TIGIT and CD155 in the effector phase, 2016, Journal of Investigative Dermatology, 136, 255-263.
[cited by applicant]
Lu et al., 2005, “In vivo application of RNA interference: from functional genornics to therapeutics,” Adv. Genet., 54:117-142.
[cited by applicant]
Ma et al., 2016, “Versatile strategy for controlling the specificity and activity of engineered T cells,” Proc. Natl. Acad. Sci. USA, 113(4):E450-E458.
[cited by applicant]
Manieri et al., 2017, “TIGIT: a Key Inhibitor of the Cancer Immunity Cycle,” Trends Immunol., 38(1):20-28 (Epub 2016).
[cited by applicant]
Milone et al., 2009, “Chimeric receptors containing CD 137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo,” Mol. Ther., 17(8): 1453-1464.
[cited by applicant]
Moore et al., Short Hairpin RNA (sh RNA): Design, Delivery, and Assessment of Gene Knockdown, Methods Mol Biol. 2010, 629: 141-158.
[cited by applicant]
Motegi et al., An effective gene-knockdown using multiple shRNA-expressing adenovirus vectors, 2011, Journal of Controlled Release, 153, 149-153.
[cited by applicant]
Neelapu et al., 2018, “Chimeric antigen receptor T-cell therapy—assessment and management of toxicities,” Nat. Rev. Clin. Oncol., 15(1):47-62 (Epub 2017).
[cited by applicant]
Non-final Office Action mailed Aug. 31, 2021 in U.S. Appl. No. 17/205,951.
[cited by applicant]
Non-final Office Action mailed Aug. 9, 2022 in U.S. Appl. No. 17/701,535.
[cited by applicant]
Non-final Office Action mailed Jul. 21, 2022 in U.S. Appl. No. 16/958,649.
[cited by applicant]
Non-final Office Action mailed Mar. 30, 2021 in U.S. Appl. No. 16/958,649.
[cited by applicant]
Russia Office Action mailed Aug. 26, 2022 in Application No. RU2020125399.
[cited by applicant]
Russia Office Action mailed Jan. 11, 2022 in Application No. RU2020125399.
[cited by applicant]
Russia search report mailed Jan. 11, 2022 in App. RU2020125399 with English translation.
[cited by applicant]
Sasidharan et al., Immune checkpoint inhibitors in cancer therapy: a focus on t-regulatory cells, e-published 2017, Immunology & Cell Biology, 96, 21-33.
[cited by applicant]
Sharma et al., 2015, “Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential,” Cell, 161(2):205-214.
[cited by applicant]
Sluijmer et al., Benign Upper Extremity Tumors: Factors Associated with Operative Treatment. Hand. 2013;8 (3):274-281, abstract only, doi: 10.1007/s11552-013-9518-5.
[cited by applicant]
Song et al., Multiple shRNA expressing vector enhances efficiency of gene silencing, BMB Reports, 41(5), 258-362.
[cited by applicant]
Stauss et al., 2007, “Monoclonal T-cell receptors: new reagents for cancer therapy,” Mol. Ther., 15(10): 1744-1750.
[cited by applicant]
Tang et al., 2020, “TGF-˜ Inhibition via CRISPR Promotes the Long-Term Efficacy of CART Cells Against Solid Tumors,” JCI Insight, 5(4):el33977 (17 pages).
[cited by applicant]
ter Brake et al., Lentiviral vector design for multiple shRNA expression and durable HIV-1 inhibition, 2008, The American Society of Gene Therapy, 16(3), 557-564.
[cited by applicant]
Topalian et al., 1987, “Therapy of cancer using the adoptive transfer of activated killer cells and interleukin-2” Acta. Haematol., 78 Suppl 1:75-76.
[cited by applicant]
Travers et al.1974, Cell pp. 97-104 RNA Polymerase-Promoter Interactions: Review Some General Principles.
[cited by applicant]
Wierz et al., 2018, “Dual PD1/LAG3 immune checkpoint blockade limits tumor development in a murine model of chronic lymphocytic leukemia” Blood, 131 ( 14): 1617-1621.
[cited by applicant]
Zhang et al., 2012, “Genetic engineering with T cell receptors,” Adv. Drug Deliv. Rev., 64(8):756-762 (Epub 2011).
[cited by applicant]
Rodriguez-Abreu , et al., Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody iragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (IL) treatment in p…
[cited by applicant]
Japan Office Action mailed Apr. 25, 2023 in App. 2022-074779.
[cited by applicant]
Canada Office Action mailed Aug. 2, 2023 in CA App. 3088234.
[cited by applicant]
EP Communication mailed Jan. 26, 2023 in EP App. 21207719.2.
[cited by applicant]
Russia Decision to Grant w/English translation mailed Feb. 1, 2023 in App. RU2020125399 .
[cited by applicant]