The technology described herein is directed to compositions and methods for modifying and controlling the activity of cells by expression of proteins from self-amplifying RNA (saRNA). Also described herein are compositions and methods for modifying and controlling the activity of cells by expression of proteins from self-amplifying RNA that is substituted with chemically modified nucleotides.

Provided herein are antibodies and chimeric priming receptors that bind PSMA and antibodies and chimeric antigen receptors that bind CA9. Also provided are systems of chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9, cells expressing such systems, and methods of use thereof.

Disclosed herein are switchable chimeric receptors, switchable chimeric receptor effector cells and chimeric receptor effector cell switches. The switchable chimeric receptor-ECs are generally T cells. The chimeric receptors have non-antibody extracellular domains that recognize a chimeric receptor binding partner on the chimeric receptor-EC switch or target cell. The chimeric receptor-ECs and switches may be used for the treatment of a disease or condition in a subject in need thereof.

The technology relates in part to methods for controlling the activity or elimination of therapeutic cells using molecular switches that employ distinct heterodimerizer ligands, in conjunction with other multimeric ligands. The technology may be used, for example to activate or eliminate cells used to promote engraftment, to treat diseases or condition, or to control or modulate the activity of therapeutic cells that express chimeric antigen receptors or recombinant T cell receptors.

The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.

The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.

Provided herein are modified caspase-9 polypeptides, and chimeric caspase-9 proteins containing the modified caspase-9 polypeptides. The disclosure further provides polynucleotides encoding these proteins, engineered host cells containing these polynucleotides and proteins, including host cells that co-express a chimeric antigen receptor, and methods of making and using the same.

The present invention relates to a molecular switch regulation type chimeric antigen receptor polypeptide, containing a humanized anti-P329G mutant scFv sequence, a hinge region/spacer region, a transmembrane region, a costimulatory signal domain, and a stimulation signal domain; an immune effector cell engineered to express the molecular switch regulation type chimeric antigen receptor polypeptide; and a method for preparing the immune effector cell. The present invention further relates to a P329G mutant antibody capable of specifically binding CLDN18.2 molecules and a method for preparing the P329G mutant antibody. A pharmaceutical combination containing the immune effector cell and the P329G mutant antibody can be used for treating diseases related to CLDN18.2, such as cancer expressing or overexpressing CLDN18.2.

The technology described herein is directed to compositions and methods for modifying and controlling the activity of cells by expression of proteins from self-amplifying RNA (saRNA). Also described herein are compositions and methods for modifying and controlling the activity of cells by expression of proteins from self-amplifying RNA that is substituted with chemically modified nucleotides.

The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.