Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo. Also disclosed are pharmaceutical compositions comprising a Cbl-b inhibitor and a cancer vaccine, as well as methods for treating cancer using a Cbl-b inhibitor and a cancer vaccine; and pharmaceutical compositions comprising a Cbl-b inhibitor and an oncolytic virus, as well as methods for treating cancer using a Cbl-b inhibitor and an oncolytic virus.

A combination cancer therapy comprising a small molecule drug conjugate (SMDC), which targets a cell-surface receptor on an immunosuppressive cell or a cancerous cell, and cytotoxic lymphocytes, which express a chimeric antigen receptor (CAR); and a method of treating a patient for cancer using the same.

Provided herein are populations of modified NK-92 cells, compositions and kits comprising the cells, and methods of making and using the populations of cells.

The invention relates to cancer therapeutics, in particular, the system of making cancer cells more susceptible to effector cells by introduction of cellular therapy targets into the cancer cells.

Embodiments of the disclosure include methods and compositions related to chimeric antigen receptors (CAR) that target chondroitin sulfate proteoglycan-4 (CSPG4). T cells transduced with a CSPG4-specific CAR are effective for inhibition of particular cancer cells that express CSPG4. In certain embodiments, the cancer is melanoma, breast cancer, head and neck cancer, mesothelioma, glioblastoma, or renal cancer.

The invention relates to cancer therapeutics, in particular, the system of making cancer cells more susceptible to effector cells by introduction of cellular therapy targets into the cancer cells.

The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an chimeric antigen receptor and bispecific antibodies in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. Certain aspects include modified T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.

Provided are engineered B lymphocytes modified to express one or several different types of microRNAs or anti-miRs where in one embodiments the lymphocytes contain multiple copy numbers of nucleic acids encoding the one or several different types of miRs or anti-miRs. Provided are compositions and methods for treating, ameliorating, or preventing a cancer cell, a breast cancer cell or a triple negative breast cancer, or a breast cancer cell that tests negative for estrogen receptors, progesterone receptors, or HER2, comprising or by administering a composition, formulation or pharmaceutical composition comprising a microRNA or anti-miR. Provided are methods for treating an inflammation, a disease, a condition, infection or cancer capable of being treated by modulation or inhibition or expression of an miRNA or anti-miRs by administering to an individual in need thereof a B lymphocyte that secretes a microRNA or anti-miR, or a B lymphocyte supernatant, extracellular vesicle or exosome having a microRNA or anti-miR.

A method of treating cancer in a subject includes contacting an enriched population of T-cells obtained from cancer or tumor draining lymph nodes ex-vivo with: an anti-CD3 antibody, an anti-CD28 antibody, and/or functional fragments thereof, and optionally a VEGF inhibitor and/or an IL-2 receptor agonist, at amounts effective to activate and expand the T-cells and administering the activated and expanded T-cells to the subject.

The present disclosure relates to compositions and methods for compositions, methods, and kits for treating cancer using chimeric antigen receptor (CAR) modified cells. Some embodiments of the present disclosure relate to an isolated nucleic acid sequence encoding CAR. The CAR may include an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain. The antigen binding domain may bind to an antigen of a non-essential organ.