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AssigneeKSQ Therapeutics, Inc.
InventorsMicah BENSON, Michael SCHLABACH, Gregory KRYUKOV, Anne Louise CADZOW, Isabelle Fleur LE MERCIER, Frank STEGMEIER
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The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.
A modified immune effector cell comprising a gene-regulating system capable of reducing expression and/or function of at least two endogenous target genes selected from SOCS1, PTPN2, and ZC3H12A, wherein the reduced expression and/or function of the at least two endogenous target genes enhances an effector function of the immune effector cell.
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A modified immune effector cell, comprising reduced expression and/or function of at least two endogenous genes selected from SOCS1, PTPN2, and ZC3H12A, wherein the reduced expression and/or function of the at least two endogenous genes enhances an effector function of the immune effector cell.
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A modified immune effector cell, comprising one or more exogenous polynucleotides encoding at least two nucleic acid inhibitors of at least two endogenous target genes selected from SOCS1, PTPN2, and ZC3H12A.
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A gene-regulating system capable of reducing expression of at least two endogenous target genes in a cell selected from SOCS1, PTPN2, and ZC3H12A, comprising (i) a nucleic acid molecule;
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A composition comprising a plurality of gRNA molecules, wherein the plurality of gRNA molecules comprises at least one gRNA molecule targeting a first target gene and at least one gRNA molecule targeting a second target gene, wherein the first and second target gene are selected from SOCS1, PTPN2, and ZC3H12A.
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A polynucleotide molecule encoding a plurality of gRNA molecules, wherein the plurality of gRNA molecules comprises at least one gRNA molecule targeting a first target gene and at least one gRNA molecule targeting a second target gene, wherein the first and second target gene are selected from SOCS1, PTPN2, and ZC3H12A.
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A polynucleotide molecule encoding a plurality of siRNA or shRNA molecules, wherein the plurality of siRNA or shRNA molecules comprises at least one siRNA or shRNA molecule targeting a first target gene and at least one siRNA or shRNA molecule targeting a second target gene, wherein the first and second target gene are selected from SOCS1, PTPN2, and ZC3H12A.
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A polynucleotide molecule encoding at least one TALEN, zinc finger, or meganuclease protein targeting a first target gene and at least one TALEN, zinc finger, or meganuclease protein targeting a second target gene, wherein the first and second target gene are selected from SOCS1, PTPN2, and ZC3H12A.
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A method of enhancing one or more effector functions of an immune effector cell comprising introducing a gene-regulating system into the immune effector cell, wherein the gene-regulating system is capable of reducing the expression and/or function of at least two endogenous target genes selected from SOCS1, PTPN2, and ZC3H12A.
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Dependencies are inferred from the claim text.