This disclosure describes chimeric antigen receptors (CARs) engineered immune cells including the CARs, pharmaceutical compositions that include engineered immune cells that include the CARs, and methods involving such engineered immune cells.

Methods of using polypeptides to modulate transforming growth factor-? (TGF?) signaling (e.g., TGF? receptors, antibodies or antigen-binding fragments thereof that specifically bind TGF? or a TGF? receptor) are provided. Compositions comprising the antibodies or fragments thereof and methods of using the same for treatment of diseases involving TGF? activity are provided. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions comprising these antigen binding agents and fragments thereof are also disclosed. The invention also provides therapeutic methods for utilizing the TGF? signaling modulators are provided herein.

Methods of using polypeptides to modulate transforming growth factor-? (TGF?) signaling (e.g., TGF? receptors, antibodies or antigen-binding fragments thereof that specifically bind TGF? or a TGF? receptor) are provided. Compositions comprising the antibodies or fragments thereof and methods of using the same for treatment of diseases involving TGF? activity are provided. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions comprising these antigen binding agents and fragments thereof are also disclosed. The invention also provides therapeutic methods for utilizing the TGF? signaling modulators are provided herein.

Embodiments of the disclosure concern methods and compositions related to cancer therapy using myeloid derived suppressor cells (MDSC) as a solo therapy or an adjunct therapy. The MDSCs are prepared by exposing bone marrow cells or blood cells to one or more compositions that induce their differentiation to MDSCs and also to TGF-?1, and in specific embodiments the exposure to TGF-?1 results in the MDSCs having anti-tumor activity and/or immune stimulatory activity.

Aspects of the disclosure relate to polypeptides comprising a signal peptide, an antigen-binding domain that specifically binds TGF-?, a peptide spacer, a transmembrane domain, and an endodomain. When expressed in a cell, the polypeptides are capable of not only neutralizing the TGF-? but also specifically triggering T-cell activation in the presence of TGF-?. T-cell activation spurs the immune cell to produce immunostimulatory cytokines and proliferate, thus turning TGF-? from an immunosuppressive signal to an activating stimulus.

Provided are a chimeric antigen receptor immune cell, and a preparation method therefor and an application thereof. The surface of the chimeric antigen receptor immune cell expresses a receptor targeting a specific antigen, and also expresses a signal conversion protein. The signal conversion protein is a fusion protein containing a dominant negative receptor TGFBR2 extracellular element and an IL-7R intracellular element. The chimeric antigen receptor immune cell can further convert, by means of the signal conversion protein, the inhibitory signal of a TGF- immunosuppressive factor in a tumor microenvironment that is not conducive to the survival of immune cells into a cytokine activation signal, thereby significantly enhancing the survival of the immune cells and having a more sustained tumor killing effect.