Tumor-specific chemoimmunotherapy of murine fibrosarcoma using tumor-specific transplantation antigen, cyclophosphamide, and interleukin-2. |
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Authors: | K Naito S Nomi H Komichi Y Ueda H Yamagishi T Oka N R Pellis B D Kahan |
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Affiliation: | Second Department of Surgery, Kyoto Prefectural University of Medicine, Japan. |
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Abstract: | 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. |
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