The present invention relates to novel multispecific antigen binding proteins that are capable of binding to multiple targets. Pharmaceutical compositions comprising the multispecific antigen binding proteins as well as methods for producing them are also disclosed.

The disclosure is directed to dual variable domain immunoglobulin double-stranded RNA conjugates that are advantageous for inhibition of target gene expression, as well as compositions suitable for therapeutic use. The dual variable domain immunoglobulin comprises a first variable domain that binds to a binding target, and a second variable domain that comprises a reactive residue, where the linker is covalently conjugated to the reactive residue. The dsRNA is linked to the linker and is capable of inhibiting the expression of the target gene by RNA interference. The disclosure also provides pharmaceutical compositions comprising these conjugate and methods of inhibiting the expression of a target gene by administering these conjugates, e.g., for the treatment of various disease conditions.

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 disclosure provides antigen binding domains that bind cluster of differentiation 3 (CD3) protein, comprising the antigen binding domains that bind CD3ε, polynucleotides encoding them, vectors, host cells, methods of making and using them.

The present invention relates to an immunocytokine comprising an heterodimeric protein complex based on IL-15/IL-15Rα, and to use thereof as a therapeutic agent, in particular as an agent for the treatment of cancer and an autoimmune disease. The present invention further relates to an immunocytokine comprising a heterodimeric protein complex based on an IL-15/IL-15Rα and an immunomodulatory antibody, and to use thereof as a therapeutic agent, in particular as an agent for the treatment of cancer and an autoimmune disease.

Provided are bispecific antibodies against CD3 and EGFR, the nucleic acid molecules encoding the antibodies, expression vectors and host cells used for the expression of the antibodies. The antibodies provide a potent agent for the treatment of CD3-related and/or EGFR-related diseases via modulating immune functions.

Provided herein are novel anti-CD28×anti-B7H3 (also referred to as “αCD28×αB7H3”) heterodimeric bispecific antibodies and methods of using such antibodies for the treatment of cancers. Subject αCD28×αB7H3 antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and targeting to B7H3 on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful for enhancing anti-tumor activity when used in combination with other anti-cancer therapies.

A polypeptide encoding a chimeric antigen receptor (CAR) comprising at least one extracellular binding domain that comprises a scFv formed by at least a VH chain and a VL chain specific to an antigen, wherein said extracellular binding domain comprises at least one mAb-specific epitope.

Provided herein are antibodies, or antigen binding portions thereof, that bind to glucocorticoid-inducible TNF receptor (GITR). Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.

The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward CLL1 positive cells. The engineered immune cells endowed with such CARs are particularly suited for immunotherapy for treating cancer, in particular leukemia.