Continuous intrasplenic interleukin-2 combined with antigen-specific chemoimmunotherapy.
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.
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006649:Histocompatibility Antigens / Q000008:administration & dosage*; D007116:Immunization, Passive; D007267:Injections; D007376:Interleukin-2 / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D010641:Phenotype; D012513:Sarcoma, Experimental / Q000276:immunology / Q000628:therapy*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; D007376:Interleukin-2; C029237:tumor-associated transplantation antigen; D003520:Cyclophosphamide