Continuous intrasplenic interleukin-2 combined with antigen-specific chemoimmunotherapy

K. Naito, N. R. Pellis and B. D. Kahan

A methylcholanthrene-induced fibrosarcoma model in C3H/HeJ mice demonstrated that combined chemoimmunotherapy, including partially purified, 1-butanol-extracted, tumor-specific transplantation antigen (1 microgram), cyclophosphamide (20 mg/kg), and continuous intrasplenic (IS) or intravenous (IV) infusion of purified human interleukin-2 (IL-2) (120 U/d) reduced the outgrowth of 4-mm established tumors, while IL-2 alone only modestly decreased tumor growth. For tumors larger than 1 cm, only the triple regimen with IS IL-2 significantly inhibited tumor growth, whereas IL-2 alone or the triple regimen with IV IL-2 failed to retard tumor growth. Furthermore, the first regimen significantly decreased pulmonary metastases after primary tumor resection. The Lyt-2+ phenotype predominated in the effector population of animals treated with this regimen, while L3T4+ cells predominated in those treated with the triple regimen that included IV IL-2. Thus, continuous IS IL-2 administration potentiates the efficacy of antigen-specific chemoimmunotherapy.