Combination of radiation and vaccination with autologous tumor cells expressing IL-2, IFN-gamma and GM-CSF for treatment of murine renal carcinoma.

BACKGROUND

We previously showed, in a murine renal cell carcinoma (RCC) model, that lung irradiation plus vaccination with autologous tumor cells producing recombinant interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (Renca/cytokine) reduces the number of lung metastases by over 90%. The present study investigates the host cellular mechanisms mediating this anti-tumor activity.

MATERIALS AND METHODS

Lung metastases were produced by injection of BALB/c mice i.v. with wild-type Renca cells (wt Renca) on day 0. The mice were then injected s.c. with irradiated Renca/cytokine vaccine cells on days 4, 8 and 11. Lungs were irradiated (300 rads) on day 7. Natural killer (NK) cells or T cells were depleted by injection i.p. with an antibody against anti-asialo GM1 or Thy1.2, respectively. Polyinosinic-polycytidylic acid (poly I:C) was injected i.p. to activate NK cells. Lung tumors were enumerated on day 21.

RESULTS

The anti-asialo GM I antibody totally abolished the antitumor activity elicited by the combined vaccination/radiation treatment regime. In contrast, anti-Thyl.2 antibody did not significantly decrease treatment efficacy. Poly I:C elicited over 95% reduction in lung metastases and strong NK activation as assayed against YAC-1 cells in vitro.

CONCLUSIONS

It appears that NK cells and granulocytes are predominantly involved in the antitumor action elicited by the cytokine-secreting autologous tumor cell vaccine in this metastatic RCC model.