Therapy with repeated intratumoral and perilymphatic administration of relatively low doses of
polyethylene-glycol(PEG)-modified
interleukin-2 (IL-2) in the syngeneic guinea pig line 10 (L10) hepatocarcinoma results in significant local
tumor growth inhibition and a delay in development of regional
lymph node metastases of more than 3 weeks when compared to controls. Occasionally animals are cured of
tumor. The mechanism of this antitumor activity was studied. The antitumor activity of locoregionally administered
PEG-IL-2 was abrogated by pretreatment with polyclonal anti-thymocyte serum, indicating that the observed
tumor growth inhibition was a T-cell-mediated phenomenon. Besides the locoregional
tumor growth inhibition, a systemic effect was recorded as the growth of a second
tumor cell inoculum at the contralateral side was inhibited as well. Furthermore, those animals cured after
PEG-IL-2 therapy developed specific immunity against the L10
tumor and this immunity could be transferred to naive animals by spleen cells. Immunohistological observations of the
tumor site revealed a slight increase of helper and cytotoxic T cell subpopulations after
PEG-IL-2 therapy. More pronounced, however, was the rise in number of eosinophilic granulocytes present in the stroma surrounding the
tumor cells. Involvement of cytotoxic cells in the antitumor effects of
PEG-IL-2 could not be demonstrated: regional lymph node cells and spleen cells obtained immediately after
therapy (day 15) or on day 21 showed no cytotoxic activity in vitro against L10, K562, Daudi and line 1 (L1) target cells. In conclusion, locoregional
therapy with
PEG-IL-2 induced a a systemic T-cell-mediated antitumor response. As no cytotoxic T cell activity was measured, however, the underlying mechanism is most likely a T-helper response. Eosinophils at the
tumor site may be tumoricidal but further experiments must reveal the role of these cells in the PEG-IL-2-induced
tumor regression.