Abstract: The present disclosure provides compositions and methods for expanding T cells or tumor infiltrating lymphocytes (TILs) in vitro. K562 feeder cells engineered to express a costimulatory molecule (e.g., 41BB ligand (41BBL)) and either interleukin 21 (IL21) or interleukin 7 (IL7) can be used in a rapid expansion protocol (REP) step to expand the T cells or TILs. Thus, provided herein is a culture comprising T-cells or TILs and modified K562 feeder cells. The T cells can be modified to express a chimeric antigen receptor (CAR) or a T cell receptor (TCR) or the TILs can be modified to express membrane-bound IL15 (mbIL15). The T cells or TILs can be expanded in vitro using aREP without the use of exogenous interleukin 2 (IL2), and the expanded cells can be used in adoptive cell therapy for treatment of cancer without concomitant use of an exogenous cytokine such as IL2.

Abstract: The present invention relates to compositions and methods for the regulated and controlled expression of proteins. Methods for inducing anti-cancer immune responses in a subject are also provided.

Abstract: The present invention provides biocircuit systems, effector modules and compositions for cancer immunotherapy. Methods for inducing anti-cancer immune responses in a subject are also provided.

Abstract: The present invention relates to compositions and methods for the regulated and controlled expression of proteins. Methods for inducing anti-cancer immune responses in a subject are also provided.

Abstract: The present disclosure provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities. In particular, the present application is directed to fusion proteins comprising a fragment of human human carbonic anhydrase 2 and a chimeric antigen receptor (CAR). The activity of the destabilizing domain can be regulated by externally administered agents.

Abstract: The present disclosure relates to tunable biocircuit systems for the development of controlled and/or regulated therapeutic systems. In particular, regulatable biocircuits containing destabilizing domains (DD) derived from mutant human cGMP-specific phosphodiesterase type 5 (PDE5) are disclosed. Especially, the present disclosure provides an effector module. Such effector module may include (a) a stimulus response element (SRE), wherein the SRE is a DD, said DD comprising at least one mutation relative to cGMP-specific 3?,5?-cyclic phosphodiesterase (hPDE5; SEQ ID NO: 1) and (b) at least one payload, which is attached, appended or associated with said SRE. The SRE may be responsive to one or more stimuli.

Abstract: The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (EL15) payloads, as well as compositions and methods of use thereof.

Abstract: The present disclosure provides regulatable biocircuit systems, effector modules and compositions for cancer immunotherapy. Methods for inducing anti-cancer immune responses in a subject are also provided.

Abstract: The present disclosure is directed to an engineered protein (e.g., a chimeric protein) comprising one or more of an extracellular domain, a transmembrane domain and/or an intracellular domain, which are capable of binding a negative signal and functioning as a sink, dominant negative, or signal inverter for the negative signal. The disclosure is further directed to methods of generating a modified cell expressing one or more of the engineered proteins (e.g., chimeric proteins), and methods of using the modified cells in treating a disease or a condition in a subject in need thereof.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of BCMA. The invention also relates to chimeric antigen receptor (CAR) specific to BCMA vectors encoding the same, and recombinant T cells comprising the BCMA CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a BCMA binding domain.

Abstract: The present invention relates to compositions and methods for the regulated and controlled expression of proteins. Methods for inducing anti-cancer immune responses in a subject are also provided.

Abstract: The present disclosure is related to compositions and methods for the regulated and controlled expression of proteins.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of BCMA. The invention also relates to chimeric antigen receptor (CAR) specific to BCMA vectors encoding the same, and recombinant T cells comprising the BCMA CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a BCMA binding domain.

Abstract: The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (IL15) payloads, as well as compositions and methods of use thereof.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD33. The invention also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain.

Abstract: The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (IL15) payloads, as well as compositions and methods of use thereof.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CD33. The invention also relates to chimeric antigen receptor (CAR) specific to CD33, vectors encoding the same, and recombinant T cells comprising the CD33 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD33 binding domain.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CLL-1. The invention also relates to chimeric antigen receptor (CAR) specific to CLL-1, vectors encoding the same, and recombinant cells comprising the CLL-1 CAR. The invention also includes methods of administering a genetically modified cell expressing a CAR that comprises a CLL-1 binding domain.

Abstract: The present invention relates to compositions and methods for the regulated and controlled expression of proteins. Methods for inducing anti-cancer immune responses in a subject are also provided.

Abstract: The invention provides compositions and methods for treating diseases associated with expression of CLL-1. The invention also relates to chimeric antigen receptor (CAR) specific to CLL-1, vectors encoding the same, and recombinant cells comprising the CLL-1 CAR. The invention also includes methods of administering a genetically modified cell expressing a CAR that comprises a CLL-1 binding domain.