The present disclosure provides compositions and methods for making and using engineered killer phagocytic cells for immunotherapy in cancer or infection by expressing a chimeric antigen receptor having an enhanced phagocytic activity, the chimeric receptor is encoded by a recombinant nucleic acid.

The present application provides constructs comprising an antibody moiety specifically recognizing Glypican 3 (GPC3), such as a cell surface-bound GPC3. Also provided are methods of making and using these constructs.

The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to chimeric antigen receptors (CARs) comprising a mutated CD28 intracellular motif, and cells comprising such CARs. The presently disclosed subject matter further relates to the use of said cells for treating diseases, e.g., for treating cancers.

The present disclosure generally relates to therapies involving immune effector cells such as T cells engineered to express antigen receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs). It is demonstrated herein that such antigen receptor-engineered immune effector cells may be generated in vitro/ex vivo as well as in vitro by delivering nucleic acid encoding an antigen receptor for genetic modification to cells using particles comprising the nucleic acid and a targeting molecule for targeting the immune effector cells, wherein the targeting molecule is a designed ankyrin repeat protein (DARPin). In particular, DARPins are described herein which are high-affinity binders for CDS binding to the CDS receptor on human and non-human primate (NHP) cells. Nanoparticles functionalized with CD8− targeting DARPins (CDS-DARPin) can deliver genes exclusively and specifically to human CD8.sup.+ T cells in vitro and in vivo.

Methods and compositions are provided related to therapeutic receptors, including chimeric antigen receptors (CARs), capable of specifically binding TYRP-1. The disclosed compositions include, for example, cells (e.g., immune cells) expressing TYRP-1 specific CARs, nucleic acids encoding TYRP-1 specific CARs, and TYRP-1 specific CAR polypeptides. Certain aspects relate to methods of treating cancer, including melanoma, using compositions comprising TYRP-1 specific CARs, for example cells expressing TYRP-1 specific CARs. In some embodiments, provided herein are chimeric polypeptides comprising a TYRP-1 binding domain, a hinge region, a transmembrane domain, and an intracellular signaling domain.

The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to cells comprising a c-Kit mutant, e.g., a c-Kit mutant comprising an activating mutation. The cells can further comprise an antigen-recognizing receptor (e.g., a chimeric antigen receptors (CAR) or a T cell receptors (TCR)). The presently disclosed subject matter relates to the use of cells for treatment, e.g., treating cancers.

This disclosure describes genetically engineered natural killer (NK) cells, pharmaceutical compositions that include these NK cells, and methods of making and using these NK cells.

There is provided a chimeric antigen receptor (CAR) comprising a CD19-binding domain which comprises a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: CDR1—GY-AFSSS (SEQ ID No. 1); CDR2—YPGDED (SEQ ID No. 2) CDR3—SLLYGDYLDY (SEQ ID No. 3); and b) a light chain variable region (VL) having CDRs with the following sequences: CDR1—SASSSVSYMH (SEQ ID No. 4); CDR2—DTSKLAS (SEQ ID No. 5) CDR3—QQWNINPLT (SEQ ID No. 6). There is also provided a cell comprising such a CAR, and the use of such a cell in the treatment of cancer, in particular a B cell malignancy.

Described herein are methods for producing and utilizing an alternative signal 1 domain to construct an optimally signaling CAR. Alternative signal 1 domains of the present technology are based on alternatives to CD3ζ, including mutated ITAMs from CD3ζ (which contains 3 IT AM motifs), truncations of CD3ζ, and alternative splice variants known as CD3s, CD3 theta, and artificial constructs engineered to express fusions between CD3s or CD30 and CD3ζ. CAR polypeptides comprising alternative signal 1 domains are utilized to engineer CAR T cells. Further, this technology related to methods of treating cancer by administering to a subject in need thereof CAR T cells comprising alternative signal 1 domains.

The present invention relates to a novel chimeric antigen receptor (CAR) comprising an antigen-binding fragment which binds specifically to PSMA antigen, and a method of manufacturing high-quality CAR T cell products by transfection and/or transduction of T cells therewith, which allows to effectively treat tumors in vivo alone or in combination with pharmaceutical drugs, such chemotherapies, biopharmaceutical drugs, such as antibodies, or small-molecule drugs, such as protein kinase inhibitors.