The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease.

The invention provides compositions and methods for treating diseases associated with expression of CD19, e.g., by administering a recombinant T cell comprising the CD19 CAR as described herein, in combination with one or more B-cell inhibitors, e.g., inhibitors of one or more of CD10, CD20, CD22, CD34, CD123, FLT-3, ROR1, CD79b, CD179b, or CD79a. The disclosure additionally features novel antigen binding domains and CAR molecules directed to CD20 and CD22, and uses, e.g., as monotherapies or in combination therapies. The invention also provides kits and compositions described herein.

Provided are methods, kits and compositions for ameliorating toxicity, such as cytokine release syndrome or neurotoxicity, suspected or being induced by or associated with, administration of a therapeutic agent, such as a immunotherapeutic agent targeting T cells and/or genetically engineered T cells, e.g. chimeric antigen receptor (CAR)-expressing T cells. The methods involve administering an additional agent, such as an agent having anti-oxidant or anti-inflammatory properties, that modulates immune cells such as by preventing or reducing the production of pro-inflammatory cytokines or stress cytokines and/or promoting differentiation to a neuroprotective phenotype, and/or capable of preventing, blocking or reducing microglial cell activation or function and/or capable of modulating, such as promoting, the activity of NRF2 or a component of an NRF2-regulated pathway, and/or one or more components involved in an antioxidant response element (ARE). The provided methods can be used in connection with or for methods of treating a disease or condition.

Provided are methods, kits and compositions for ameliorating toxicity, such as cytokine release syndrome or neurotoxicity, suspected or being induced by or associated with, administration of a therapeutic agent, such as a immunotherapeutic agent targeting T cells and/or genetically engineered T cells, e.g. chimeric antigen receptor (CAR)-expressing T cells. The methods involve administering an additional agent, such as an agent having anti-oxidant or anti-inflammatory properties, that modulates immune cells such as by preventing or reducing the production of pro-inflammatory cytokines or stress cytokines and/or promoting differentiation to a neuroprotective phenotype, and/or capable of preventing, blocking or reducing microglial cell activation or function and/or capable of modulating, such as promoting, the activity of NRF2 or a component of an NRF2-regulated pathway, and/or one or more components involved in an antioxidant response element (ARE). The provided methods can be used in connection with or for methods of treating a disease or condition.

The present invention provides a method of carrying out adoptive immunotherapy in a primate subject in need thereof by administering the subject a cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount. The method comprises administering as the CTL preparation a preparation consisting essentially of an in vitro expanded primate CTL population, the CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes. In some embodiments, the method may further comprise concurrently administering Interleukin-15 to the subject in an amount effective to increase the proliferation of the central memory T cells in the subject. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

Disclosed herein are chimeric antigen receptor effector cells (CAR-ECs) and CAR-EC switches. The switchable CAR-ECs are generally T cells. The one or more chimeric antigen receptors may recognize a peptidic antigen on the CAR-EC switch. The CAR-ECs and switches may be used for the treatment of a condition in a subject in need thereof.

The present disclosure relates to compositions and methods relating to chimeric antigen receptor (CAR) polypeptides and methods relating thereto. In one embodiment, the present disclosure relates to engineered cells having chimeric antigen receptor polypeptides directed to at least two targets. In another embodiment, the present disclosure relates to engineered cells having chimeric antigen receptor polypeptides and an enhancer moiety.

The present invention provides compositions and methods for transducing cells (e.g. T cells or immune cells). Also provided herein are methods of treating a disease in a subject in need thereof.

An aspect of the invention provides nucleic acids comprising a nucleotide sequence encoding chimeric antigen receptor (CAR) amino acid constructs. Polypeptides, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CAR constructs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

The present invention relates to the field of biomedicine, to an improved T cell receptor-costimulatory molecule chimera, in particular to a T cell receptor (TCR) or TCR complex comprising a costimulatory molecule, a T cell comprising the TCR or TCR complex, and the use thereof.