The present invention provides compositions and methods for inducing a CAR mediated trans-signal in a T cell. The trans-signaling CAR T cells comprise a first CAR having a first signaling module and a second CAR having a distinct second signaling module. The present invention also provides cells comprising a plurality of types of CARs, wherein the plurality of types of CARs participate in trans-signaling to induce T cell activation.

Some embodiments of the present disclosure are directed to methods that include delivering to a subject a papillomavirus particle or soluble papillomavirus protein that targets a tumor, and delivering to the subject an immune cell expressing a receptor that binds to a surface antigen of the papillomavirus particle or soluble papillomavirus protein, respectively.

The present invention relates to methods of treating a proliferative disease (such as cancer) in an individual, comprising administering to the individual a non-naturally occurring fusion molecule comprising an antibody against one or more tumor-associated antigen (TAA Ab) attached to an interferon (IFN) molecule (hereinafter TAA Ab-IFN fusion molecule), as monotherapy at therapeutically effective low doses, or in combination with immunotherapy, wherein the combination therapy provides increased effector cell killing. The methods of the present invention are particularly effective treating recurrent, resistant, or refractory proliferative diseases.

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein.

The present invention generally embraces the treatment of diseases by targeting cells expressing an antigen on the cell surface. In particular the invention relates to recombinant antigen receptors and uses thereof. T cells engineered to express such antigen receptors are useful in the treatment of diseases characterized by expression of one or more antigens bound by the antigen receptors.

The present invention relates to humanized HER2 single domain antibodies and variants thereof and their use in therapy and for cancer diagnosis. The invention most particularly proposes chimeric antigen receptors including said humanized HER2 sdAb in their antigen binding domain and their use in cancer cell therapy.

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.

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 herein are recombinant nucleic acids encoding chimeric priming receptors that bind ALPG/P, chimeric antigen receptors that bind MSLN, and shRNA that target FAS, PTPN2, and/or TOX. Also provided are systems of chimeric priming receptors that bind ALPG/P, chimeric antigen receptors that bind MSLN, and shRNA that target FAS, PTPN2, and/or TOX, cells expressing such proteins and shRNA, and methods of use thereof.