Disclosed herein are methods and compositions for cell-based immunotherapies that simultaneously target the tumor microenvironment (TME) via NKG2D ligands and tumor cells via tumor-associated antigens, specifically using immune effector cells as the platform due to their reduced toxicity against normal tissue. In some embodiments, immune effector cells co-express an NKG2D cytotoxic CAR and a CAR directed against a tumor-associated antigen that provides costimulatory signals to the immune effector cell, thus killing only in the presence of both antigens specifically within the TME. In contrast, within normal tissue that might express the tumor-associated antigen, but where self-HLA is also expressed, the costimulatory signal by itself is insufficient for immune effector cell activation, thereby preventing off-tumor toxicity.

An immune effector cell expressing an exogenously introduced p40 subunit of IL-12; an exogenously introduced ligand of CCR7 (such as CCL-19 and CCL-21); and a functional exogenous receptor (such as a chimeric antigen receptor) comprising an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain.

In certain aspects, the disclosure relates to an immune cell that has been engineered to comprise one or more heterologous polynucleotides that promote thanotransmission by the immune cell. The immune cell may also comprise one or more nucleic acid sequences that encode a chimeric antigen receptor (CAR). Methods of promoting thanotransmission, promoting immune response, and treating cancer using the engineered immune cells are also disclosed.

A multiple myeloma-specific CAR+ T-cell composition and a vaccine composition composed of 3 cells lines, the U266, H929, and K562 are described. Methods are described for using the vaccine composition in conjunction with the MM-specific CAR+ T cell composition in methods of immunizing against plasma cell disorders, including multiple myeloma and related disorders.

Human iPSC-derived macrophages, methods for the manufacture thereof, and methods of treatment of cancer and other conditions therewith. Human iPSC-derived macrophages further comprise a chimeric antigenic receptor (CAR) expressed thereon, such as Bai1, MegF10 or MerTK, referred to as iPSC-derived CAR-expressing macrophages (iPSC-CARMAs). The methods of treatment provide further co-administering to the subject an effective amount of iPSC-CARMAs and an antibody specific for the cancer, such as anti-CD47 or anti-EGFR antibody. The iPSC-derived macrophages promote phagocytic activity, reduce tumor burden, and improve subject survival.

A method for producing natural killer cells is disclosed. The method comprises isolating peripheral blood mononuclear cells (PBMCs) from a blood sample; isolating at least one of CD56+ cells and/or CD3?/CD56+ cells from the PBMCs; and co-culturing the at least one of CD56+ cells and/or CD3?/CD56+ cells with a combination of feeder cells in the presence of a cytokine. A composition for treating cancer is also disclosed. The composition comprises the CD56+ natural killer cells produced by the disclosed method and a cytokine.

This disclosure describes, generally, a modified form of CD16, genetically-modified cells that express the modified CD16, and methods that involve the genetically-modified cells. The modified form of CD16 can exhibit increased anti-tumor and/or anti-viral activity due, at least in part, to reduced susceptibility to ADAM17-mediated shedding upon NK cell stimulation.

Provided are single-domain antibodies targeting CLL1 and constructs thereof, including chimeric receptors, immune effector cell engagers and immunoconjugates. Further provided are engineered immune effector cells (such as T cells) comprising an anti-CLL1 chimeric receptor and optionally a second chimeric receptor targeting a second antigen or epitope. Pharmaceutical compositions, kits and methods of treating cancer are also provided.

The present invention relates to the field of biomedicines. Specifically, the present invention relates to a chimeric antigen receptor (CAR) targeting EGFR, a CAR-T cell containing the CAR, as well as a preparation method and use thereof.

The present invention provides compositions and methods for inhibiting one or more diacylglycerol kinase (DOK) isoform in a cell in order to enhance the cytolytic activity of the cell. In one embodiment, the cells may be used in adoptive T cell transfer. For example, in some embodiments, the cell is modified to express a chimeric antigen receptor (CAR). Inhibition of DOK in T cells used in adoptive T cell transfer increases cytolytic activity of the T cells and thus may be used in the treatment of a variety of conditions, including cancer, infection, and immune disorders.