Methods and compositions for treating cancer, particularly improved CAR-T methods, are disclosed.

Disrupting convergence of lytic granules produced by cytotoxic lymphocytes allows non-directional degranulation, which improves and broadens killing efficiency of the cytotoxic cells in pathogenic environments such as when used for cancer therapy. Accordingly, methods of inducing multidirectional degranulation by cytotoxic effector cells in a tumor microenvironment, methods of treating a tumor, and related therapeutic composition are described.

The present disclosure provides methods for treating cancer and/or delaying or decreasing cytokine release syndrome in a patient in need thereof comprising administering an effective amount of dexamethasone and an effective amount of tumor-specific T cell engaging multi-specific antibodies. Kits for use in practicing the methods are also provided.

The present disclosure provides methods for treating cancer and/or delaying or decreasing cytokine release syndrome in a patient in need thereof comprising administering an effective amount of dexamethasone and an effective amount of tumor-specific T cell engaging multi-specific antibodies. Kits for use in practicing the methods are also provided.

The present invention relates to an in vitro method for priming genetically modified T cells suitable for administration to a patient having a tumor. The invention is also directed to the composition obtained by the method and uses thereof.

The present invention concerns immunotherapy for cancers having cells that comprise the ganglioside GD2 antigen. In specific embodiment, T cells having a chimeric receptor that targets GD2 is employed. In particular cases, the chimeric receptor comprises antibody, cytoplasmic signaling domain from the T cell receptor, and/or costimulatory molecule(s).

The present disclosure provides chimeric antigen receptors, compostions, and methods thereof. In one embodiment the present disclosure provides a method of treating autoimmune diseases, asthma, and preventing or mediating organ rejection in a subject.

Disclosed herein are modified NKTs expressing human IL-12, compositions comprising the modified NKTs, and therapeutic methods for using the modified NKTs. The modified NKTs described herein are reprogrammed NKTs that demonstrate long term persistence when the expression of IL-12 is coupled with the expression of a CAR. These NKTs acquire long-term capacity to eliminate tumor cells and long-term persistence of NKTs expressing IL-12. Also disclosed herein are modified cells transformed to express a CAR and an exogenous membrane-bound moiety, such as IL-12.

An isolated human NKT cell or a plurality of cells thereof, having reduced or no detectable expression of endogenous beta-2-microglobulin (B2M); endogenous MHC class II-associated invariant chain (Ii); or both. Methods to generate the cell or cells, and methods of treatment using the cell or cells are also provided.

The present invention relates to a cell which comprises; (i) a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and (ii) a chimeric TNF receptor (TNFR) which comprises (a) a binding domain which is capable of binding a TNFR ligand; and (b) a TNFR signalling domain.