5 results about "Transforming growth factor beta" patented technology

This invention relates to a fusion protein that specifically binds to the extradomain B of fibronectin (EDB-FN) and transforming growth factor β (TGFβ), and its uses. More specifically, it relates to a fusion protein comprising a polypeptide that specifically binds to EDB-FN and a polypeptide that specifically binds to TGFβ, and its uses. The fusion protein of this invention achieves direct localization of TGFβ inhibition within the tumor microenvironment by immobilizing TGFβ, which is important for anti-tumor immune responses, in the extracellular matrix, ensuring local rather than systemic action. It not only exhibits excellent anti-tumor effects in various cancer types, but also, due to the rigidity of the extracellular matrix, demonstrates excellent anti-tumor effects in pancreatic cancer, where traditional TGFβ inhibitors are ineffective. Therefore, it can be usefully applied to the prevention or treatment of cancer.

The present invention is based on the seminal discovery that targeted immunomodulatory antibodies and fusion proteins can counter act or reverse immune tolerance of cancer cells. Cancer cells are able to escape elimination by chemotherapeutic agents or tumor-targeted antibodies via specific immunosuppressive mechanisms in the tumor microenvironment and such ability of cancer cells is recognized as immune tolerance. Such immunosuppressive mechanisms include immunosuppressive cytokines (for example, Transforming growth factor beta (TGF-β)) and regulatory T cells and / or immunosuppressive myeloid dendritic cells (DCs). By counteracting tumor-induced immune tolerance, the present invention provides effective compositions and methods for cancer treatment, optional in combination with another existing cancer treatment. The present invention provides strategies to counteract tumor-induced immune tolerance and enhance the antitumor efficacy of chemotherapy by activating and leveraging T cell-mediated adaptive antitumor immunity against resistant or disseminated cancer cells.

RNA molecules comprising a guide sequence portion having 17-50 contiguous nucleotides in the sequence set forth in any one of SEQ ID NOs: 1-2860 and compositions, methods, and uses thereof.

The present invention relates to novel polypeptides, which are derived from transforming growth factor beta 1 (TGFβ1; TGFb-1) as well as polynucleotides encoding such polypeptides and compositions comprising such peptides. The present invention is further concerned with ways to increase the selectivity of the immune response to TGFb-1. The invention also concerns uses, and methods of using, said polypeptides, polynucleotides, and compositions.

The present disclosure relates to T cells engineered to comprise a heterologous nucleic acid sequence encoding a dual mutant transforming growth factor beta 1 (dmTGFB1) under control of a promoter sequence and a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TGFBR2. In certain embodiments, the cells further comprise a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TNFA; a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding an IFNG; and insertion of sequence(s) encoding a regulatory T cell promoting molecule, and compositions and uses thereof.