Provided are compositions and methods for a cell population comprising engineered cytotoxic innate lymphoid cells engineered for controlled expansion and/or activity, the engineered cytotoxic innate lymphoid cells comprising a synthetic cytokine receptor for a non-physiological ligand. The cytokine receptor may comprise a synthetic gamma chain polypeptide as a first dimerization domain, a first transmembrane domain, and an interleukin-2 receptor subunit gamma (IL-2RG) intracellular domain and a synthetic beta chain polypeptide as a second dimerization domain, a second transmembrane domain, and an intracellular domain selected from an interleukin-2 receptor subunit beta (IL-2RB) intracellular domain, an interleukin-7 receptor subunit beta (IL-7RB) intracellular domain, and/or an interleukin-21 receptor subunit beta (IL-21RB) intracellular domain. The non-physiological ligand activates the synthetic cytokine receptor in the cytotoxic innate lymphoid cells to induce expansion and/or activation of the engineered cytotoxic innate lymphoid cells.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Described are chimeric lactate receptors that act a molecular switches. A chimeric lactate receptor comprises a lactate receptor linked to one or more intracellular signaling domains. Also described are nucleic acids encoding the chimeric lactate receptors, T cell expressing the chimeric lactate receptors, and method of using the T cells to treat cancer.

The present invention relates to an antibody or antigen-binding fragment thereof that targets cotinine, a chimeric antigen receptor comprising same, and uses thereof. The antibody of the present invention is an antibody that specifically binds to cotinine, and in particular, an antibody that binds more specifically to the S-isomer of cotinine than to the R-isomer thereof. In addition, the antibody has very low homology and a unique sequence, compared to the CDR sequences of conventional cotinine target antibodies. Cells expressing a chimeric antigen receptor comprising the anti-cotinine antibody or antigen-binding fragment of the present invention bind to a cotinine-conjugated switch and respond to a target cell line, thereby inducing immune cell activity. Therefore, the antibody or antigen-binding fragment thereof of the present invention can be used to suppress immune side effects due to overactivation of T cells through cotinine-mediated activation regulation of chimeric antigen receptor effector cells.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

A chimeric antibody receptors with anti-cotinine antibodies linked, and uses thereof are disclosed. A T cell presenting the chimeric antibody receptor on the surface secretes interferon gamma specifically for a target molecule of a cotinine-conjugated binding molecule that is added together therewith and induces cell death of the cell expressing the target molecule by the T cell. On the contrary, by administering a cytotoxic agent conjugated with cotinine, cell death of the chimeric antigen receptor T cell is induced. Therefore, if necessary, a cytotoxic agent conjugated with cotinine can be administered to remove the chimeric antigen receptor T cells that have been already administered, thereby suppressing immune side effects due to hyperactivity of T cells. Thus, the chimeric antigen receptor to which the anti-cotinine antibody is linked can be effectively and safely used for the treatment of cancer.

Described are T-cells that express a multivalent CLTX-CAR and also express a survival factor, a population of the T-cells that express a multivalent CLTX-CAR and the survival factor, pharmaceutical compositions thereof, and methods of treating cancer or a tumor in a subject comprising administering to a subject an effective amount of the multivalent CLTX-CAR T-cells and co-administering a chemotherapeutic agent, e.g., the chemotherapeutic agent to which the survival factor confers resistance.