Inhibition of TGFβ1 Makes Nonimmunogenic Tumor Cells Effective for Therapeutic Vaccination

Abstract

We have previously demonstrated that transplanted cells from the SW1 clone of the K1735 melanoma and the Ag104 sarcoma grow progressively in syngeneic C3H mice even after transfection to engage CD137, a procedure that increases the immunogenicity of many other tumors. We now show that SW1 and Ag104 cells produce high levels of transforming growth factor (TGF) beta1, and that they can induce an antitumor response if they are transfected with a nonreplicating lentivirus vector to "silence" the TGFbeta1 gene via short hairpin RNA. Importantly, vaccination with SW1 or Ag104 cells, which do not make TGFbeta1, is therapeutically efficacious against small wild type tumors, including SW1 micrometastases in the lung. An analogous approach may be applicable to human tumors that produce TGFbeta1 or other immunosuppressive molecules to improve the efficacy of tumor cell-based therapeutic vaccines.