Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. III. Postoperative activation of tumor-specific CTLP from mice with metastases requires stimulation with the specific antigen plus additional signals.

DBA/2 mice transplanted with the high metastatic syngeneic lymphoma variant ESb can be successfully treated by a combination of surgery and active-specific immunotherapy (ASI). The ASI procedure was applied postoperatively and involved vaccination either (1) with inactivated ESb tumor cells which had been modified by incubation with a low dose of Newcastle Disease Virus (NDV) or (2) with mutagenesis-derived immunogenic tumor variants. The analysis of the immune status of spleens from tumor-bearing or tumor-immune mice revealed important differences. The activation of tumor-specific cytotoxic T-lymphocyte precursors (CTLP) from mice with metastasis required stimulation with the specific antigen plus additional helper factors (IL-2 or NDV). The importance of second signal immune stimulation for the activation of sensitized tumor-specific CTLP in tumor-bearing mice is underlined.