The present invention relates to compositions and methods that provide novel therapies in cancer. The invention includes a phagocytic cell modified with a repressor of signal regulatory protein-alpha (SIRP) and bound to a targeting antibody to enhance phagocytic activity of the phagocytic cell toward tumor tissue. Methods of enhancing phagocytic activity and treating a tumor are also included.

Antigen-binding agents such as antibodies or antigen-binding fragments thereof, chimeric antigen receptors (CARs), bispecific T-cell engagers (BiTEs) and the like that specifically bind to epidermal growth factor receptor variant III (EGFRvIII) are provided. The EGFRvIII-specific antibodies or antigen-binding fragments, CARs and BiTEs thereof may be used for the treatment of cancer. Antibody drug conjugates targeting EGFRvIII-expressing cells are particularly contemplated.

Provided herein are compositions, methods, and uses involving bispecific binding molecules that specifically bind to HER2, a receptor tyrosine kinase, and to CD3, a T cell receptor, and mediate T cell cytotoxicity for managing and treating disorders, such as cancer. Also provided herein are uses and methods for managing and treating HER2-related cancers.

This invention provides a method for maximizing the immune response to mutated tumor specific proteins, either by means of stimulation of dendritic cells or T cells in vitro followed by administration of these cells to a patient, or by means of administration of a neoantigen vaccine in which de novo peptides, or their encoding nucleic acids, have been designed to ensure an appropriate level of binding affinity to a particular cancer patient's MHC alleles. This invention further provides for modulating the immune response in an immunopathology other than cancer.

Provided herein are compositions, methods, and uses involving bispecific binding molecules that specifically bind to HER2, a receptor tyrosine kinase, and to CD3, a T cell receptor, and mediate T cell cytotoxicity for managing and treating disorders, such as cancer. Also provided herein are uses and methods for managing and treating HER2-related cancers.

An object of the present invention is to provide EGFR CAR-T cells expected to be effective for tumors expressing EGFR. The present invention provides a polynucleotide encoding a chimeric antigen receptor (CAR) protein having a target-binding domain that binds to epidermal growth factor receptor (EGFR), a transmembrane domain, and an intracellular signaling domain, wherein the target-binding domain is a ligand for EGFR, and a vector comprising the polypeptide, and a genetically modified cell having the polypeptide or the vector introduced thereinto.

The present disclosure relates to antigen-binding agents that specifically bind to epidermal growth factor receptor variant III (EGFRvIII). Antigen-binding agents of the present disclosure include antibodies and antigen-binding fragments thereof, chimeric antigen receptors (CARs) and bi-specific T-cell engagers (BiTE!), bispecific killer cell engagers (BiKEs) and trispecific killer cell engagers (TrikEs). Nucleic acid molecules and vectors expressing antibodies, antigen-binding fragments. CARs, BiTEs, BiKEs or TriKEs are also encompassed by the present disclosure. Immune cells engineered to express CARs, BiTEs, BiKEs or TriKEs may be used to specifically recognize and kill cells expressing EGFRvIII.

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated EGFR amino acid sequence with a E746-A750 deletion. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

The present invention relates to the adoptive therapy using notably CAR-T cells. Here the inventors used a lentiviral vector approach to silence RINF expression in a shRNA-dependent manner and evaluate the consequences of RINF silencing on human CAR-T cells proliferation ex vivo and their functionality and capacity to eradicate tumor cells in vivo. More, the proposed methodology to improve CAR-T cells persistence and efficacy by disrupting RINF/CXXC5 is not restricted to patients suffering from hematological or solid cancers (anti-CD19, anti-EGFR, anti-BCMA . . . ) but could be also used to improve the efficacy of ACT in non-cancer diseases by such as lupus (1), cardiac fibrosis (2) or aging related-disorders (3). Thus, the present invention relates to an immune cell characterized in that it is defective for RINF.

The present disclosure relates to an engineered T-cell Receptors (TCRs) capable of binding to an epitope of an epidermal growth factor receptor (EGFR) comprising a T790M mutation presented on human leukocyte antigen-A (HLA-A)*02:01, wherein the epitope comprises the amino acid sequence of MQLMPFGCLL (SEQ ID NO: 1). Also disclosed are Tcell and BiTE therapies comprising the same, and methods of treating EGFR-TKI resistant lung cancers using the same.