Provided herein are methods of treating a subject who has multiple myeloma and has received one to three prior treatment(s). Infusions of chimeric antigen receptor (CAR)-T cells comprising a CAR capable of specifically binding to an epitope of BCMA are administered to the subject.

Provided by the disclosure are compositions and methods for modulating differentiation of regulatory T cells. In some embodiments, methods include selectively decreasing IL-23R activity and/or IL-23R expression without significantly decreasing IL-12R activity and/or IL-12R expression.

The invention relates to the field of CAR-T cell immunotherapy, more specifically the invention relates to production and uses of glyco-engineered CAR-T cells for the improvement of immunotherapy compositions for treatment of cancer, more specifically of solid tumors. The invention specifically relates to human CAR-T cells with a mutated MGAT5 gene, as to provide for surface glycan structures devoid of tetra-antennary N-glycans, which results in a sustained memory when applied in immunotherapy, to cure cancer, reduce (recurrent) tumor growth and tumor burden, as well as to prevent relapse. The invention further relates to methods for manufacturing of those CAR-T cells, wherein addition of low amounts of DMSO during activation and expansion ex vivo skews T cell populations to a more predominant memory phenotype, thereby providing for improved glycol-engineered CAR-T cell compositions for adoptive T cell transfer.

Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer.

An isolated immune regulatory cell having an exogenous cell death-inducing moiety attached to a surface thereof is disclosed herein. Additionally, a molecule comprising a cell death-inducing moiety heterologously attached to an immune regulatory cell-specific binding moiety is disclosed herein. Methods of generating and using same as well as pharmaceutical compositions comprising same are also disclosed.

Compositions and methods for binding to target antigens. Compositions comprising variable heavy chain domains with binding specificity to CD70, GPC3, IL13Ralpha2 and Cadherin CDH17 antigens.

Modified T cells comprising ectopic CD40 proteins (such as chimeric CD40 proteins including a CD40 extracellular domain and a heterologous intracellular domain) are provided. Also provided are compositions, including pharmaceutical formulations, comprising the modified T cells, and methods for increasing T cell-mediated tumor cell-specific cytotoxicity using the same. Methods of treating a subject with cancer including administering to the subject the modified T cells, thereby activating an innate immune response and/or an adaptive immune response in the subject are also provided.

The disclosure provides CARs (CARs) that specifically bind to CD70. The disclosure further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The disclosure further relates to therapeutic methods for use of these CARs and engineered immune cells comprising these CARs for the treatment of a condition associated with malignant cells expressing CD70 (e.g., cancer).

A population of genetically engineered T cells, comprising a disrupted Reg1 gene and/or a disrupted TGFBRII gene. Such genetically engineered T cells may comprise further genetic modifications, for example, a disrupted CD70 gene. The population of genetically engineered T cells exhibit one or more of (a) improved cell growth activity; (b) enhanced persistence; and (c) reduced T cell exhaustion, (d) enhanced cytotoxicity activity, (e) resistant to inhibitory effects induced by TGF-b, and (f) resistant to inhibitory effects by fibroblasts and/or inhibitory factors secreted thereby, as compared to non-engineered T cell counterparts.

Described herein are methods and compositions for regulatory T cells (Tregs) that are modified to express a chimeric antigen receptor (CAR) that targets OX40L. Aspects of the invention relate to administering these modified Tregs to a subject having an inflammatory or autoimmune condition.