Shinhachiro Nomi

Active Specific Chemoimmunotherapy of Lymph‐node Metastasis from a Poorly Immunogenic Murine Fibrosarcoma

The fibrosarcoma MCA‐SP, which was recently induced with methylcholanthrene (MCA) in C3H/ HeJ mice, displays poor immunogenicity in in vivo prophylaxis. A cell variant MCA‐SPN1, which bears a tumor‐specific transplantation antigen (TSTA) cross‐reactive with the parental line MCA‐SP, was selected because of its proclivity for axillary lymph‐node metastases. Although these lymph‐node metastases were resistant to sinecomitant (post‐excisional) immunity, they were susceptible to combined active and passive specific Chemoimmunotherapy, using tumor‐specific, 1‐butanol‐extracted, preparative isoelectric focusing‐purified, TSTA (1 fig weekly sc injections), cyclophosphamide (CY, a single intraperitoneal 20 mg/kg dose), and adoptive transfer of immune splenic T lymphocytes, which had been re‐stimulated in vitro with extracted TSTA and interleukin‐2. This triple regimen both reduced the incidence of spontaneous lymph‐node metastases, and prolonged the survival of tumor‐bearing, as well as tumor‐resected hosts. The results from local adoptive transfer assay using T‐lymphocyte snbpopulations of spleen and lymph nodes in these treated hosts suggested that Lyt 2+ cytotoxic T‐lymphocytes (CTL) mediated in vivo tumor‐neutralization. Thus TSTA/CY/CTL therapy activates tumoricidal host responses effective against the poorly immunogenic MCA‐SP tumor and its lymph‐node metastases.