Gene activation and interference targets for exhaustion/dysfunctionresistant t cell products and uses thereof
AssigneesThe J. David Gladstone Institutes, a Testamentary Trust Established Under the Will of J. David Glads, The Regents of the University of California
InventorsZachary Steinhart, Alexander Marson
Life of this patent
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Abstract
Provided herein are gene activation and interference targets for exhaustion/dysfunction-resistant t cell products and uses thereof.
Claims21
A modified T cell, lymphoid cell or myeloid cell comprising a modification of one of more genes selected from BATF, CUL3, CLASRP, CDKL3, EOMES, FOXL2NB, FOXO6, FOXO4, FOSB, FOSL1, FOXL2, GLIS3, GL2, IRF4, IL2RA, INPP5D, IL2RB, ITPKA, ITPKB, HL10, IL9R, LIFR, LCK, LYN, NPM3, NQO1, PLEKHH3, PTEN, RFLNB, STAT5A, SHOC2, S100A13, TRAF3IP2, TMEM167B, TSR2, VAV1 or ZNF211, wherein the modification upregulates or increases expression of said gene in said modified T cell, lymphoid cell or myeloid cell as compared to a non-modified T cell, lymphoid cell or myeloid cell control.
A modified T cell, lymphoid cell or myeloid cell comprising a modification of one of more of genes selected from CCNC, ELOB, ELOC, IGFL4, MED1, MED12 MED13, MN1, MED19, MEOX1, MOCS3, NQO2, PRDM14, SYCE1L, SYTL2, SRRD, SPIN1, UBF2E1, ARHGAP5, ARIH1, ARIH2, ATF7IP, ATF7IP2, ATXN7L3, BORCS8, CAND1, CASP3, CBFB, CDK13, CDKN2A, CFAP54, CISH, COPS7B, CPSF4L, CUL5, CUTA, DCUN1D3, DDA1, GABARAPL1, KDM5C, KIAA1551, KRTAP10-9, MADD, MAPKAP1, MED23, MED24, MYB, MYO5A, NFKBIA, PAK2, PDCL, PIK3R5, PTEN, RASA2, RNASE9, RNF7, RPS6KAI, SBNO2, SND1, ST8SIA5, TNIP1, TRIM56, TSPEAR, UBAP2L, UBE2F, UBE2L3, WDFY1, ZBTB21 or ZMYND8, wherein the modification downregulates or decreases expression of said gene in said modified T cell, lymphoid cell or myeloid cell as compared to a non-modified T cell, lymphoid cell or myeloid cell control.
A method comprising ex vivo modification of any of the genes listed in Table 1 within at least one T cell, lymphoid cell or myeloid cell, or a combination thereof to generate at least one modified T cell, lymphoid cell, myeloid cell, or a mixture of modified T cells, lymphoid cells and myeloid cells.
-24. (canceled)
A method to overcome T cell exhaustion comprising upregulating one or more genes selected from BATF, CUL3, CLASRP, CDKL3, EOMES, FOXL2NB, FOXO6, FOXO4, FOSB, FOSL1, FOXL2, GLIS3, GLI2, IRF4, IL2RA, INPP5D, IL2RB, ITPKA, ITPKB, IL10, IL9R, LIFR, LCK, LYN, NPM3, NQO1, PLEKHH3, PTEN, RFLNB, STAT5A, SHOC2, S100A13, TRAF3IP2, TMEM167B, TSR2, VAV1 or ZNF211 or downregulating one or more genes selected from CCNC, ELOB ELOC, IGFL4, MED1, MED12, MED13, MN1, MED19, MEOX1, MOCS3, NQO2, PRDM14, SYCE1L, SYTL2, SRRD, SPIN1, UBE2E1, ARHGAP5, ARIH1, ARIH2, ATF7JP, ATF7IP2, ATXN7L3, BORCS8, CAND1, CASP3, CBFB, CDK13, CDKN2A, CFAP54, CISH, COPS7B, CPSF4L, CUL5, CUTA, DCUN1D3, DDA1, GABARAPL1, KDM5C, KIAA1551, KRTAP10-9, MADD, MAPKAP1, MED23, MED24, MYB, MYO5A, NFKBIA, PAK2, PDCL, PIK3R5, PTEN, RASA2, RNASE9, RNF7, RPS6KA1, SBNO2, SND1, ST8SIA5, TNIP1, TRIM56, TSPEAR, UBAP2L, UBE2F, UBF2L3, WDFY1, ZBTB21 or ZMYND8 in a T cell, lymphoid cell, myeloid cell.
Dependencies are inferred from the claim text.