Abstract: Disclosed are compositions comprising an isolated chimeric interleukin 6 receptor alpha (IL-6R?) binding protein or cells expressing an isolated chimeric IL-6R? binding protein. The isolated IL-6R? chimeric binding protein and cells expressing the protein may be used in methods of treating cancer and reducing the risk of cytokine release syndrome.

Abstract: The current disclosure provides for novel multi-specific CAR molecules for the treatment of glioblastoma (also called GBM or glioblastoma multiforme). This disclosure also describes nucleic acids encoding for the polypeptides, expression vectors comprising the nucleic acids, cells and/or populations of cells expressing the polypeptides and/or comprising the nucleic acids or expression vectors of the disclosure, and compositions comprising the polypeptides, nucleic acids, or cells.

Abstract: The current disclosure provides for novel multi-specific CAR molecules for the treatment of glioblastoma (also called GBM or glioblastoma multiforme). This disclosure also describes nucleic acids encoding for the polypeptides, expression vectors comprising the nucleic acids, cells and/or populations of cells expressing the polypeptides and/or comprising the nucleic acids or expression vectors of the disclosure, and compositions comprising the polypeptides, nucleic acids, or cells.

Abstract: Disclosed are compositions comprising an isolated chimeric interleukin 6 receptor alpha (IL-6R?) binding protein or cells expressing an isolated chimeric IL-6R? binding protein. The isolated IL-6R? chimeric binding protein and cells expressing the protein may be used in methods of treating cancer and reducing the risk of cytokine release syndrome.

Abstract: Aspects of the disclosure relate to novel scFv molecules that are useful for incorporation into novel chimeric antigen receptors with enhance anti-tumor activity. Further aspects relate to a polypeptide comprising a CAR comprising, in order from amino proximal to carboxy proximal end, a scFv, a transmembrane domain, a torsional linker, and a cytoplasmic region comprising a primary intracellular signaling domain, wherein the torsional linker comprises 1-12 alanine residues. Also described are nucleic acids comprising a sequence encoding a polypeptide of the disclosure, vectors, such as lentiviral vectors comprising the nucleic acids of the disclosure, cells comprising and/or expressing nucleic acids and/or polypeptides of the disclosure, and populations of cells comprising the cell embodiments of the disclosure. Also provided are methods of making cells that express a polypeptide and methods of treating patients with the polypeptides and cell compositions of the disclosure.

Abstract: The current disclosure provides polypeptide, nucleic acid, compositions, and methods for treating or preventing CRS in patients in need thereof, particularly for those receiving an immunotherapy, such as a cancer immunotherapy, that may provoke a CRS response. Accordingly, aspects of the disclosure relate to a chimeric binding polypeptides comprising a heavy chain variable region comprising CDR1, CDR2, and CDR3 attached by a heterologous linker to a light chain variable region comprising CDR4, CDR5, and CDR6.

Abstract: 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.

Abstract: Methods and compositions are provided concerning a bispecific chimeric antigen receptor (CAR) targeting BCMA and CS1, particularly in multiple myeloma patients. The bispecific CAR has advantages over dual or separate BCMA and CS1 CAR molecules. In some embodiments, there is a bispecific chimeric antigen receptor comprising a) a bispecific extracellular binding domain comprising both i) a BCMA-binding region and ii) a CSI-binding region; b) a single transmembrane domain; and, c) a single cytoplasmic region comprising a primary intracellular signaling domain.

Abstract: 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.

Abstract: Disclosed are compositions comprising an isolated chimeric interleukin 6 receptor alpha (IL-6R?) binding protein or cells expressing an isolated chimeric IL-6R? binding protein. The isolated IL-6R? chimeric binding protein and cells expressing the protein may be used in methods of treating cancer and reducing the risk of cytokine release syndrome.

Abstract: 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.