Abstract: The present disclosure relates to methods and compositions related to Natural Killer T cells that are engineered to harbor an expression construct that encodes an activator of the Wnt signaling pathway. Activation by expression of Wnt signaling activators or the addition of exogenous activators promotes NKT expansion over the course of multiple tumor cell challenges and improves long term tumor control in vitro. The present disclosure further includes NKT cells, populations, and methods to prepare them, that are engineered to express exogenous activators of Wnt signaling combined with chimeric antigen receptors (CARs) for therapeutic use.

Abstract: TNFR2-expressing neuroblastoma cells activate monocytes via contact-dependent mTNF? signaling, leading to production of sTNF? and IL-6 by monocytes that in turn bind to TNFR1 and IL-6R on neuroblastoma cells and stimulate tumor growth via activation of NF-?B and Sta3 signaling pathways. Growing tumor recruit additional monocytes resulting in a self-promoting inflammation that fuel tumor growth. TNF inhibitors can terminate this feed-forward signal amplification loop and inhibit tumor growth. Embodiments of the disclosure include a method of using TNF inhibitors for the treatment of neuroblastoma in a subject in need thereof. Also disclosed herein is a method of a method of using TNF inhibitors for reducing tumor-promoting inflammation in an individual with cancer.

Abstract: Embodiments of the disclosure include methods and compositions for producing NKT cells effective for immunotherapy and also methods and compositions for providing an effective amount of NKT cells to an individual in need of immunotherapy. In specific embodiments, the NKT cells are CD62L+ and have been exposed to one or more costimulatory agents to maintain CD62L expression. The NKT cells may be modified to incorporate a chimeric antigen receptor, in some cases.

Abstract: Embodiments of the disclosure include methods and compositions for producing NKT cells effective for immunotherapy and also methods and compositions for providing an effective amount of NKT cells to an individual in need of immunotherapy. In specific embodiments, the NKT cells are CD62L+ and have been exposed to one or more costimulatory agents to maintain CD62L expression. The NKT cells may be modified to incorporate a chimeric antigen receptor, in some cases.

Abstract: Embodiments of the disclosure encompass methods and compositions related to cancer treatment with particular immune effector cells as adoptive immunotherapy and/or with soluble proteins to which the immune effector cells are able to bind. In some cases, the soluble proteins are molecular adaptors that allow targeting of cancer cells that lack expression of a tumor antigen to which the adoptive immunotherapy is directed. In some embodiments, the soluble proteins are exogenously provided as cytokine-cytokine receptor pairs that improve adoptive immunotherapy.

Abstract: The present invention regards methods and/or compositions related to Natural Killer T cells that are engineered to harbor an expression construct that encodes IL-2, IL-4, IL-7, and/or IL-15 and additionally or alternatively comprise a chimeric antigen receptor (CAR). In specific embodiments, the CAR is a CAR that targets the GD2 antigen, for example in neuroblastoma.

Abstract: The present invention regards methods and/or compositions related to Natural Killer T cells that are engineered to harbor an expression construct that encodes IL-2, IL-4, IL-7, and/or IL-15 and additionally or alternatively comprise a chimeric antigen receptor (CAR). In specific embodiments, the CAR is a CAR that targets the GD2 antigen, for example in neuroblastoma.

Abstract: 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.

Abstract: Embodiments of the disclosure include methods and compositions for producing NKT cells effective for immunotherapy and also methods and compositions for providing an effective amount of NKT cells to an individual in need of immunotherapy. In specific embodiments, the NKT cells are CD62L+ and have been exposed to one or more costimulatory agents to maintain CD62L expression. The NKT cells may be modified to incorporate a chimeric antigen receptor, in some cases.

Abstract: Embodiments of the disclosure include methods and compositions for producing NKT cells effective for immunotherapy and also methods and compositions for providing an effective amount of NKT cells to an individual in need of immunotherapy. In specific embodiments, the NKT cells are CD62L+ and have been exposed to one or more costimulatory agents to maintain CD62L expression. The NKT cells may be modified to incorporate a chimeric antigen receptor, in some cases.

Abstract: Embodiments of the disclosure include methods and compositions related to immunotherapy that targets glypican-3. In particular embodiments, immune cells engineered to comprise a chimeric antigen receptor that targets glypican-3 are contemplated, and uses thereof. In particular embodiments, medical conditions that are associated with glypican-3 expression or an overexpression of glypican-3 are treated with GPC3 CARs.

Abstract: Embodiments of the disclosure include methods and compositions for producing NKT cells effective for immunotherapy and also methods and compositions for providing an effective amount of NKT cells to an individual in need of immunotherapy. In specific embodiments, the NKT cells are CD62L+ and have been exposed to one or more costimulatory agents to maintain CD62L expression. The NKT cells may be modified to incorporate a chimeric antigen receptor, in some cases.

Abstract: The present invention regards methods and/or compositions related to Natural Killer T cells that are engineered to harbor an expression construct that encodes IL-2, IL-4, IL-7, and/or IL-15 and additionally or alternatively comprise a chimeric antigen receptor (CAR). In specific embodiments, the CAR is a CAR that targets the GD2 antigen, for example in neuroblastoma.