Inhibition of TGFbeta1 makes nonimmunogenic tumor cells effective for therapeutic vaccination.
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.
Liu
Pu
P
Department of Pathology, Harborview Medical Center, University of Washington, 325 9th Avenue, Box 359939, Seattle, WA 98104, USA.
Jaffar
Jade
J
Zhou
Yifeng
Y
Yang
Yi
Y
Hellström
Ingegerd
I
Hellström
Karl Erik
KE
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D014611:Vaccination
D019496:Cancer Vaccines; D053773:Transforming Growth Factor beta1