The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g. a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.

Disclosed herein are antibodies that specifically bind and inhibit the action of the IL-6 family member LIF that are useful in the treatment of cancer. Also disclosed herein are uses of said antibodies for the treatment of cancer.

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.

An anti-B-cell maturation antigen (BCMA)/anti-4-1BB bispecific antibody or an antigen-binding fragment thereof, and use thereof, are provided. The bispecific antibody or an antigen-binding fragment thereof may have high binding affinity to both of a BCMA protein and a 4-1BB protein and may be effectively used to prevent or treat a disease related to BCMA, 4-1BB, or both thereof (e.g., cancer).

Described herein are bispecific antibodies simultaneously targeting both CHI3L1 and the immune checkpoint molecule CTLA4. These antibodies manifest enhanced synergistic cytotoxic effects compared to the effects of individual CHI3L1 and CTLA4 antibodies, alone or in combination. Methods of treating tumors, including lung and brain tumors by administering the bispecific antibodies described herein are also provided.

Methods of expanding T cells ex vivo comprising contacting the T cells with antibody molecules that bind to TCR Vβ regions are described. T cells comprise one or more nucleic acid molecule encoding an exogenous cellular receptor, for example, a chimeric antigen receptor (CAR) or an exogenous T cell receptor (TCR).

The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to cells comprising a c-Kit mutant, e.g., a c-Kit mutant comprising an activating mutation. The cells can further comprise an antigen-recognizing receptor (e.g., a chimeric antigen receptors (CAR) or a T cell receptors (TCR)). The presently disclosed subject matter relates to the use of cells for treatment, e.g., treating cancers.

The present invention is intended to provide: an anti-hCDCP1 antibody, which can be used as an active ingredient of anticancer agents having few side effects, etc.; and the aforementioned anti-hCDCP1 antibody that is formulated into ADC. Specifically, the present invention relates to an antibody that binds to human CDCP1 (CUB domain-containing protein 1), which has low binding property to human CD34-positive cells, or an antigen-binding fragment thereof. A representative example of the present antibody may be an antibody having heavy chain CDR1 comprising the amino acid sequence as set forth in SEQ ID NO: 25, heavy chain CDR2 comprising the amino acid sequence as set forth in SEQ ID NO: 26, heavy chain CDR3 comprising the amino acid sequence as set forth in SEQ ID NO: 27, light chain CDR1 comprising the amino acid sequence as set forth in SEQ ID NO: 29, light chain CDR2 comprising the amino acid sequence as set forth in SEQ ID NO: 30, and light chain CDR3 comprising the amino acid sequence as set forth in SEQ ID NO: 31.

Regulatory T cells (T.sub.reg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4.sup.+ T.sub.reg cells have been described—naturally occurring T.sub.reg cells and adaptive T.sub.reg cells. Disclosed herein are methods for producing efficacious CAR T.sub.reg cells in a GMP-scalable system.

This document provides methods and materials for assessing a mammal having or suspected of having cancer and/or for treating a mammal having cancer. For example, molecules including one or more antigen-binding domains (e.g., a single-chain variable fragment (scFv)) that can bind to a modified peptide (e.g., a tumor antigen), as well as method for using such molecules, are provided.