Effect of recombinant human IL-12 and anti-IL-12 on human lung tumor xenografts in SCID mouse

The anti-tumor activity of human IL-12 and the effects of anti-IL-12 were evaluated in a human-SCID mouse chimeric model in which non-disrupted pieces of human non-small cell lung cancer (NSCLC) biopsy tissue were engrafted into SCID mice. We observed a co-engraftment of tumor and tumor infiltrating lymphocyte (TIL) in these mice. Tumor growth was monitored weekly by estimating tumor volumes, the presence of TIL was confirmed and the level of activity estimated by quantifying human immunoglobulin (HuIg) in the sera of the tumor inoculated scid mice. Treatment of mice with hIL-12 increased serum levels of HuIg and provoked a TIL-dependent suppression of the growth of human tumor xenografts. Mice treated with antibodies to IL-12 significantly enhanced the growth of human tumor xenografts established following the inoculation of fresh tumor biopsy tissue. Neither hIL-12 nor anti-IL-12 had any direct effect upon growth of a human NSCLC cell line in scid mice. These results are consistent with the notion that human IL-12, either produced locally within the tumor TIL xenograft, or given exogenously, provokes or enhances a TIL mediated anti-tumor response in vivo, and establishes the potential of this cytokine as a therapeutic agent for human lung cancer.