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.