Local
polyethylene-glycol (PEG)-modified
interleukin-2 (IL-2)
immunotherapy of the guinea pig Line 10 (L10)
tumor was previously demonstrated to evoke long-lasting systemic immunity after cure of the
tumor and
metastases. T cells, most likely the helper T cell subpopulation, were demonstrated to be crucial to the antitumor effects. Here we show that systemic immunity is induced within 7 days after the start of
PEG-IL-2 therapy, indicating a rapid systemic priming of L10-specific T cells. No in vitro cytotoxic activity was detected in cell
suspensions obtained from the primary
tumor site, the regional lymph node or the spleen when isolated during (days 21 and 28) intratumoral treatment with 200,000 IU
PEG-IL-2. These data confirm our earlier results obtained with 60,000 IU
PEG-IL-2. Moreover, no cytolytic activity was observed in the
chromium-release assay after in vitro restimulation with irradiated
tumor cells. Specific L10 immunity can be transferred using spleen cell
suspensions. Depletion of such a
suspension of helper T cells resulted in rejection of the primary
tumor in two out of four animals, but all the guinea pigs developed
lymph node metastases. Removal of the cytotoxic/suppressor phenotype caused rejection of the dermal
tumor in four of eight guinea pigs, but the capacity to prevent
lymph node metastases was retained in all animals. Thus, depletion of either subtype reduces, but does not abrogate, the capacity to transfer L10 immunity with spleen cells. In conclusion, our data suggest that
tumor cell killing through direct T cell cytotoxicity is not the main mode of action in PEG-IL-2-induced L10
tumor regression.
PEG-IL-2 therapy induces early systemic immunity, resulting in rejection of a distant
tumor, and the transfer of this immunity depends mainly on the presence of helper T cells, although cytotoxic T cells may also play a role.