Tumor-specific chemoimmunotherapy of murine fibrosarcoma using tumor-specific transplantation antigen, cyclophosphamide, and interleukin-2.
The anti-tumor effect of active specific chemoimmunotherapy, using butanol-extracted tumor-specific transplantation antigen (TSTA), cyclophosphamide (CY), and continuous intrasplenic infusion of interleukin-2 (IS-IL-2), was assessed in a C3H/HeJ murine methylcholanthrene (MCA)-induced fibrosarcoma model. Sole administration of TSTA induced tumor-specific, suppressor T cells in the spleens of mice bearing 3-day established tumors. Concomitant low-dose (20 mg/kg) CY treatment not only inhibited TSTA-mediated suppressor cell induction, but also evoked splenic lymphocytes of tumor-bearing mice to display tumor-specific cytotoxic activity. High-dose (200 mg/kg) CY abrogated the immunotherapeutic benefit. The immune effectors generated by TSTA plus CY bear the Thy 1, L3T4, Lyt 2 phenotype. Continuous IS-IL-2 infusion in combination with TSTA and CY induced tumor-specific Lyt 2+ cytolytic T cells, as well as the activation of L3T4+ cytostatic T cells. Thus, a triple regimen using TSTA, CY, and IS-IL-2 appears to augment CTL induction in tumor-bearing hosts undergoing stimulation of helper elements by TSTA and inhibition of suppressor cells by CY.
Second Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
K
K
Naito
S
S
Nomi
H
H
Komichi
Y
Y
Ueda
H
H
Yamagishi
T
T
Oka
N R
NR
Pellis
B D
BD
Kahan
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D005260:Female; D005354:Fibrosarcoma / Q000628:therapy*; D006649:Histocompatibility Antigens / Q000276:immunology*; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000166:cytology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; D007376:Interleukin-2; C029237:tumor-associated transplantation antigen; D003520:Cyclophosphamide