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.