Treatment of Established Renal Cancer by Tumor Cells Engineered to Secrete Interleukin-4

TLDR

Cancer immunotherapy aims to generate antigen‑specific antitumor immunity. Engineered renal tumor cells secreting IL‑4 were rejected in a T‑cell–independent manner yet induced a systemic, CD8⁺‑mediated, tumor‑specific immune response that cured established tumors, supporting lymphokine gene‑transfected tumor cells as a therapeutic strategy.

Abstract

The generation of antigen-specific antitumor immunity is the ultimate goal in cancer immunotherapy. When cells from a spontaneously arising murine renal cell tumor were engineered to secrete large doses of interleukin-4 (IL-4) locally, they were rejected in a predominantly T cell-independent manner. However, animals that rejected the IL-4-transfected tumors developed T cell-dependent systemic immunity to the parental tumor. This systemic immunity was tumor-specific and primarily mediated by CD8 + T cells. Established parental tumors could be cured by the systemic immune response generated by injection of the genetically engineered tumors. These results provide a rationale for the use of lymphokine gene-transfected tumor cells as a modality for cancer therapy.