The present application provides methods and compositions for treating cancers using a CAR T cell therapy platform. Also provided are methods and use of the CAR T cells for treating diseases and conditions, such as cancer, and in particular any disease or condition associated with elevated adenosine or other associate marker.

The neuroblastoma immunopeptidome is enriched with peptides derived from proteins essential for tumorigenesis including the unmutated peptide QYNPIRTTF (SEQ ID NO: 1) discovered on HLA-A*24:02 which is derived from the neuroblastoma dependency gene and master transcriptional regulator PHOX2B. To target QYNPIRTTF, peptide-centric chimeric antigen receptors (PC-CARs) were developed via a counter panning strategy using predicted potentially cross-reactive peptides. Informed by computational modeling, PHOX2B peptide centric CARs were demonstrated to also recognize QYNPIRTTF (SEQ ID NO: 1) presented by HLA-A*23:01 and the highly divergent HLA-B*14:02. Potent and specific killing of neuroblastoma cells expressing these HEAs in vitro was shown along with complete tumor regression in mice.

The present application provides BCMA targeting chimeric antigen receptor (CAR) comprising a BCMA binding region and an intracellular costimulatory domain derived from DAP10. Further provided are engineered immune effector cells (such as NK cells) comprising the chimeric antigen receptors. Pharmaceutical compositions, kits and methods of treating cancer are also provided.

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.

This document relates to methods and materials involved in treating cancer. For example, methods and materials for using one or more oncolytic viruses (OVs) in combination with an adoptive cell therapy (e.g., a chimeric antigen receptor T cell therapy) to alter one or more functions of a T cell and/or to enhance T cell expansion to treat cancer in a mammal (e.g., a human) are provided.

Provided herein are antibodies that specifically bind to GPRC5D. Also described are related polynucleotides capable of encoding the provided GPRC5D-specific antibodies or antigen-binding fragments, cells expressing the provided antibodies or antigen-binding fragments, as well as associated vectors and detectably labeled antibodies or antigen-binding fragments. In addition, methods of using the provided antibodies are described. For example, the provided antibodies may be used to diagnose, treat, or monitor GPRC5D-expressing cancer progression, regression, or stability; to determine whether or not a patient should be treated for cancer; or to determine whether or not a subject is afflicted with GPRC5D-expressing cancer and thus may be amenable to treatment with a GPRC5D-specific anti-cancer therapeutic, such as the multispecific antibodies against GPRC5D and CD3 described herein.

The disclosure provides methods for improved hematopoietic stem cell transplantations, including methods to enhance protection from graft versus host disease while maintaining effective immune responses such as graft versus tumor immune responses. The disclosure provides methods for administering, for example, hematopoietic stem and progenitor cells, regulatory T cells, and conventional T cells, wherein the conventional T cells are administered after the hematopoietic stem and progenitor cells and regulatory T cells. The disclosure also provides methods for administering, for example, hematopoietic stem and progenitor cells, regulatory T cells, and conventional T cells, wherein the regulatory T cells have not been cryopreserved prior to administration.

The present invention relates to the recognition of CSF1R as a marker of hematological cancer and thus relates to CSF1R targeting agents for the treatment of such cancers, in particular, AML. The invention also relates to a lymphocyte recombinantly expressing a chimeric antigen T cell receptor (CAR) specific for CSF1R, in particular, for use in the treatment of cancer characterized by the expression of colony stimulating factor 1 receptor (CSF1R). The present invention further relates to a CAR comprising an extracellular domain that specifically binds CSF1R, a transmembrane domain, and an intracellular T cell activating domain; as well as polynucleotides, vectors and host cells used in the production of the CAR. Further, methods for the production of such lymphocytes and a pharmaceutical composition comprising such lymphocytes are provided. The cells of the invention are preferably human lymphocytes and more preferably primary human lymphocytes such as CD3+ T cells, CD8+ T cells, CD4+ T cells, ?? T cells, invariant T cells or NK T cells.

The present disclosure provides improved T cell receptors, polynucleotides, polypeptides, vectors, cells, and methods of using the same. Particularly, the present invention relates to T cell receptor-based constructs engineered to comprise one or more additional binding domains, and methods of using the same. In certain embodiments, the one or more binding domains are fused to one or both TCR variable domains. In particular embodiments, the one or more additional binding domains are linked to the TCR with one or more polypeptide linkers.

The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy for the treatment of cancer with a KRAS mutation with TILs as described herein in combination with KRAS inhibitors.