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 provides multivalent CD20-binding molecules, and compositions thereof, such as enriched compositions comprising large proportions of multivalent CD20-binding molecule relative to monovalent CD20-binding molecule. Certain multivalent CD20-binding molecules of the present invention comprise 1) two or more CD20 binding regions and 2) one or more Shiga toxin effector polypeptide regions derived from an A Subunit of a member of the Shiga toxin family. Certain multivalent CD20-binding molecules of the present invention, and compositions thereof, have uses for selective killing specific cell types and as therapeutics for the treatment of a variety of diseases, including cancers, tumors, and immune disorders. Certain multivalent CD20-binding molecules of the present invention, and compositions thereof, have uses for delivering agents into CD20-expressing cells, including for the intracellular labeling of CD20-expressing cells, collecting diagnostic information, and monitoring the treatment of variety diseases, such as cancers, tumors, and immune disorders which involve CD20-expressing cells.

A chimeric antigen receptor (CAR) comprising an extracellular spacer which comprises at least part of the extracellular domain of human low affinity nerve growth factor (LNGFR) or a derivative thereof.

The present disclosure provides compositions and methods for boosting, augmenting or enhancing the efficacy of the adoptive cellular immunotherapy by using modified T cells expressing an antigen binding protein in conjunction with modified cells (such as hematopoietic progenitor cells, modified human immune system cells or a combination thereof) expressing the antigen specifically bound by the antigen binding protein of the modified T cells.

Embodiments of the disclosure include compositions and methods effective for immunotherapy, such as for cancer. The embodiments include cells that recognize a combination of two signals or three signals present at the tumor microenvironment. In certain embodiments, the signals for antigen stimulation, co-stimulation, and cytokine signaling act through separate molecules, although in certain embodiments the signals for antigen stimulation and co-stimulation are transmitted through the same molecule.

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

The invention generally relates to immunotherapy using immune cells such as chimeric antigen receptor (CAR)-engineered T cells. In particular, the invention relates to immunotherapy using chimeric antigen receptor (CAR)-engineered T cells that carry a novel, IgG3-Hinge-based spacer domain, allowing a finely modulated response to target antigens. In addition, the invention relates to the introduction of one or more IgG3-Hinge-based multi-function sites (MFs) into CARs and other immunoreceptors, allowing purification, stimulation, expansion and depletion of CAR T cells. The invention includes also the sequence of an antibody targeting this motif, allowing the execution of the before-mentioned functions.

The present invention provides a combined chimeric antigen receptor targeting CD19 and CD20 and application thereof. Specifically, the present invention provides a combined chimeric antigen receptor targeting CD19 and CD20, which comprises a scFv targeting CD19 and CD20, a hinge region, a transmembrane region, and an intracellular signaling domain. The present invention provides a nucleic acid molecule encoding the chimeric antigen receptor and a corresponding expression vector, a CAR-T cell, and applications thereof. The experimental results show that the chimeric antigen receptor provided by the present invention shows extremely high killing ability against tumor cells. The chimeric antigen receptor of the present invention targets CD19 and/or CD20 positive cells and can be used to treat CD19 and/or CD20 positive B-cell lymphoma, leukemia and other diseases.

Provided herein are multivalent CD20-binding molecules, and compositions thereof, for use in selective killing of specific cell types and/or as therapeutics for the treatment of a variety of diseases, including cancer, tumors, and immune disorders. Certain multivalent CD20-binding molecules can be used to deliver agents into CD20-expressing cells, collecting diagnostic information, and/or monitoring the treatment of diseases, such as cancers, tumors, and immune disorders.

The present application relates, in part, to agents that bind CD20 and their use as therapeutic agents. The present application further relates to pharmaceutical compositions comprising the CD20 binding agents and their use in the treatment of various diseases.