This disclosure relates to compositions and methods for treating cancer using chimeric antigen receptor T cells and/or antigen binding domains targeting CLDN18.2.

Memory-like cytokine enhanced NK (M-CENK) cells have superior cytotoxicity and can be generated/expanded from a single batch of mononuclear cells to in sufficient quantities to so form a cell-based therapeutic suitable for infusion. Advantageously, the M-CENK cells can be cryopreserved and thawed without compromising viability and cytotoxicity.

The present invention relates to a novel chimeric antigen receptor comprising a CD99 region which participates in immune synapse stabilization as a backbone of the chimeric antigen receptor, an immune cell comprising the same, and the uses thereof. CD99-based CAR-T cells are capable of forming very stable immune synapses with tumor cells compared to conventional backbone-based CAR-T cells and can exhibit improved tumor therapeutic efficiency, so they can be useful for immune cell therapy for the treatment of cancer.

The technology described herein is directed to Natural Killer (NK) cell CAR polypeptides comprising intracellular signaling domains, intracellular costimulatory domains, and/or transmembrane domains from NK-associated polypeptides. In various aspects, described herein are polynucleotides, vectors, or cells expressing said NK CAR polypeptides, and pharmaceutical compositions comprising said NK CAR polypeptides, polynucleotides, vectors, or cells. Also described herein are methods of using said NK CAR polypeptides, for example to treat various diseases and disorders, such as cancer or infectious diseases.

Disclosed herein are fibroblast activation protein (FAP)-specific binding polypeptides. These binding polypeptides may be incorporated into chimeric antigen receptors (CARs). Also disclosed herein are methods of using these binding polypeptides and/or CARs for the treatment of, for example, a cancer.

Disclosed are compositions and methods for targeted treatment of CLEC12A-expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill CLEC12A-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a CLEC12A-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs. Also disclosed are multivalent antibodies are disclosed that are able to engage T-cells to destroy CLEC12A-expressing malignant cells.

Provided are chimeric antigen receptors (CARs) having antigenic specificity for B-cell Maturation Antigen (SLAMF7). Also provided are related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs. Methods of treating or preventing cancer in a mammal are also provided.

A chimeric antigen receptor (CAR) comprising (1) an extracellular portion of Fms-related tyrosine kinase 3 ligand (FLT3L) that binds to Fms-related tyrosine kinase 3 (FLT3), (2) a transmembrane domain, (3) a costimulatory signaling domain, and (4) an intracellular signaling domain. A nucleic acid sequence encoding the CAR. A vector and cell comprising the nucleic acid sequence encoding the CAR. A cell expressing the CAR. A composition of cells expressing the CAR. A method of administering the composition of cells expressing the CAR to a subject for stimulating in the subject an immune response against cells which express FLT3.

A chimeric antigen receptor (CAR) having an antigen binding domain capable of binding to extracellular domains of human GnRH receptor. The antigen binding domain can have a binding affinity and specificity similar to the GHR-106 antibody. Methods of making and using such CARs are provided. The CARs can be used to treat cancer.

Natural Killer (NK) cells and NK cell lines are modified to increase cytotoxicity, wherein the cells and compositions thereof have a use in the treatment of cancer. Modified NK cells and NK cell lines are produced via genetic modification of CD38.sup.low NK cells to transiently express the Fc receptor CD16 (F158V) from mRNA introduced into the NK cell, rather than from a chromosomal coding sequence. The cytotoxicity of the modified NK cells against CD38-expressing cancer cells is increased by administration of these modified cells in combination with a CD38-binding antibody. Separately, cytotoxicity against breast cancer is exhibited by the modified NK cells in combination with

Herceptin.