Untreated Distant Tumors Research Articles

Peri-tumor interleukin-2 causes systemic therapeutic effect via interferon-γ induction

This study compares the direct local therapeutic effects of multiple peri-tumor injections of interleukin-2 (IL-2) and interferon gamma (IFN-gamma), also the associated systemic therapeutic effects on distant untreated tumors resulting from the peritumor injections. The therapeutic effects were tested against intramammary implants of an immunogenic, syngeneic C3H mammary carcinoma. Peritumor IL-2 and IFN-gamma had nearly equal local and systemic therapeutic effects. In a comparison of the therapeutic effects of IL-2 and IFN-gamma injected systemically, only the IFN-gamma injections resulted in a significant number of cures. IL-2 and IFN-gamma did not have an additive effect when used in combination, suggesting that they have connected, rather than separate, paths of action in the anti-tumor immune response. The injection of anti-IFN-gamma-MAb abrogated the systemic therapeutic effect of peri-tumor IL-2, indicating that the systemic therapeutic effect was the result of IFN-gamma induction at the IL-2 injection site.

Tumor regression at an untreated site during immunotherapy of an identical distant tumor.

The effects of two immunotherapy regimens on the development of an untreated, uniformly lethal transplantable line-10 hepatoma in strain 2 guinea pigs were monitored during treatment of an identical tumor 10 cm away. Line-10 cells were injected intradermally simultaneously at each of two sites. When one site was treated 6 and 16 days later with rabbit antibody against guinea pig fibrin fragment E, the complete regression of the treated tumor, a 25--30% depression in the development of the untreated tumor, and an increased survival time were observed. In another group of animals, when one site was treated 5 days after tumor challenge with syngeneic or xenogeneic "tumor-immune" RNA in a regimen including syngeneic nonsensitive lymphoid cells and tumor-specific antigen, all animals survived after complete and apparently specific regression of the tumors at both the treated and untreated sites. For the RNA regimen, we have shown that immunotherapy of an intradermally established line-10 tumor results in complete abrogation of both the treated and a distant untreated tumor; i.e., demonstrating a systemic effect.