Provided herein are chimeric antigen receptors (CARs) comprising a truncated EGFRvIII (Ev3) in the hinge region of the CAR and/or a humanized scFv. Further provided herein are immune cells expressing the CARs as well as methods of their use in the treatment of immune disorders.

The disclosure relates to a dual vector system with a first vector comprising a sequence encoding an inhibitory receptor and a sequence encoding a first part of an activator receptor; and a second vector, comprising a sequence encoding a second part of the activator receptor.

A composition and method of ex vivo producing natural killer (NK) cells expressing a chimeric antigen receptor (CAR) or a transgenic T cell receptor (tg-TCR) capable of binding HER2 is disclosed. The method comprising: (a) expanding a population of NK cells by a method comprising: (i) culturing the population of NK cells under conditions allowing for cell proliferation, wherein the conditions comprise providing an effective amount of nutrients, serum, IL-15 and nicotinamide; and (ii) supplementing the population of NK cells with an effective amount of fresh nutrients, serum, IL-15 and nicotinamide 5-10 days following step (i) to produce expanded NK cells; so as to obtain an ex vivo expanded population of NK cells, and (b) upregulating expression of a CAR or a tg-TCR capable of binding HER2 in the ex vivo expanded population of NK cells.

CAR T cells for treating CD19+, CD20+ OR CD22+ tumors, including leukemia and lymphoid malignances, provide increased safety in the therapy of the tumors and prevent epitope masking in CAR+ B-cell leukemia blasts. The CAR T cells decrease the potential risk of CD19?/CAR+, CD20?/CAR+ or CD22?/CAR+ leukemic relapse. In addition, the CAR T cells provide increased safety in the treatment of autoimmune diseases caused by B cells producing auto-antibodies.

The invention provides antigen binding domains that bind myeloid cell surface antigen CD33 protein comprising the antigen binding domains that bind CD33, polynucleotides encoding them, vectors, host cells, methods of making and using them.

Disclosed herein are chimeric antigen receptors (CARs) that target MUC1*. In some embodiments, the CARs have been optimized to reduce T cell exhaustion.

The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In embodiments the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain, a polynucleotide comprising a customized spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain. It has been surprisingly found that the length of the spacer region can affects the ability of chimeric receptor modified T cells to recognize target cells in vitro and affects in vivo efficacy of the chimeric receptor modified T cells. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

A chimeric antigen receptor (CAR), a cell (particularly an immune cell such as a regulatory T cell) expressing said CAR, a nucleic acid or vector encoding said CAR and various uses of said CAR, cell, nucleic acid or vector is disclosed herein. Particularly, a chimeric antigen receptor (CAR) comprising an antigen recognition domain that specifically binds to ENTPD3, is provided.

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 a method for stimulating, priming and/or expanding in vivo T cells genetically modified to express a chimeric antigen receptor (CAR) targeted to an antigen, comprising contacting the T cells with the antigen or a variant thereof in vivo. In one embodiment, the antigen or variant thereof is provided by administering a nucleic acid encoding the antigen or variant thereof.

This document provides methods and materials involved in binding a binder (e.g., an antibody, antigen binding fragment, antibody domain, CAR, cell engager, and/or ADC) to a PRTG polypeptide. For example, binders (e.g., antibodies, antigen binding fragments, antibody domains, CARs, cell engagers, and/or ADCs) that bind to a PRTG polypeptide and methods and materials for using one or more such binding molecules to treat a mammal (e.g., a human) having cancer are provided.