Gene-regulating compositions and methods for improved immunotherapy
Inventors
Benson, Micah • Merkin, Jason • Kryukov, Gregory V. • Shenker, Solomon Martin • Schlabach, Michael • Tubo, Noah • Kaberna, II, James Martin
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11261428-B2
Publication Date
2022-03-01
Expiration Date
Abstract
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.
Core Innovation
The invention relates to modified immune effector cells that comprise an inactivating nucleic acid mutation in an endogenous ANKRD11 gene, where endogenous ANKRD11 gene expression and/or function in the modified immune effector cell is reduced relative to endogenous ANKRD11 gene expression and/or function in an unmodified immune effector cell. In certain implementations, the modified immune effector cell also includes additional inactivating nucleic acid mutations in one or more specified endogenous target genes.
The modified immune effector cell can be defined by quantitative reduction in endogenous target gene expression and/or function, including reduction by at least 50% relative to an unmodified immune effector cell. In addition, the modified immune effector cell can include an increase in effector function, including increased effector function by at least 10% relative to an unmodified immune effector cell.
The invention also includes a gene-regulating system capable of introducing an inactivating nucleic acid mutation in an endogenous ANKRD11 gene. The gene-regulating system can use one or more nucleic acid molecules selected from siRNA, shRNA, microRNA (miR), antagomiR, and antisense RNA, or can use one or more enzymatic proteins selected from zinc finger nuclease and TALEN, or can use guide RNAs (gRNAs) and a Cas endonuclease.
Claims Coverage
The document provides two independent claims, covering a modified immune effector cell with an inactivating ANKRD11 nucleic acid mutation that reduces ANKRD11 expression and/or function, and a gene-regulating system for introducing an inactivating nucleic acid mutation in an endogenous ANKRD11 gene using RNAi/antisense, ZFN/TALEN nuclease proteins, or gRNA/Cas endonuclease components.
Modified immune effector cell with reduced endogenous ANKRD11 expression and/or function
A modified immune effector cell comprising an inactivating nucleic acid mutation in an endogenous ANKRD11 gene, wherein endogenous ANKRD11 gene expression and/or function in the modified immune effector cell is reduced relative to endogenous ANKRD11 gene expression and/or function in an unmodified immune effector cell.
Gene-regulating system for introducing an inactivating nucleic acid mutation in endogenous ANKRD11
A gene-regulating system capable of introducing an inactivating nucleic acid mutation in an endogenous ANKRD11 gene comprising one or more nucleic acid molecules selected from an siRNA, an shRNA, a microRNA (miR), an antagomiR, and an antisense RNA; one or more enzymatic proteins selected from a zinc finger nuclease and a transcription-activator-like effector nuclease (TALEN); or one or more guide RNAs (gRNAs) and a Cas endonuclease.
Overall claim coverage is centered on modified immune effector cells carrying an inactivating nucleic acid mutation in an endogenous ANKRD11 gene that reduces ANKRD11 expression and/or function, together with gene-regulating systems configured to introduce the inactivating ANKRD11 mutation using RNAi/antisense nucleic acids, ZFN/TALEN enzymatic proteins, or gRNAs with a Cas endonuclease.
Stated Advantages
Documented Applications
No documented applications found
Interested in licensing this patent?