Effect of Active Immunization with Irradiated Tumour Cells on Specific Serum Inhibitors of Cell-mediated Immunity in Patients with Disseminated Cancer

The sera from patients with advanced cancer were tested for their specific inhibitory effects on the cytotoxicity of autologous lymphocytes on tumour cells in a microculture assay. By adding a standard volume of the sera to suspensions of well-washed lymphocytes the inhibitory effect was quantitated by comparison with the effect of normal allogeneic serum. Significant levels of inhibitory activity were detected in 7 patients (one massive primary melanoma, 4 with disseminated melanoma, one with metastatic hypernephroma and one with a recurrent leiomyosarcoma). The patient with a massive primary melanoma was treated by extensive surgical excision. This procedure was associated with the rapid and complete disappearance of the serum inhibitory effect. In the other cases surgical intervention was minimal and the serum inhibitor was unaffected. All 6 of these patients were then immunized with irradiated autologous tumour cells and the serum inhibitory activity assayed. In 5 cases the serum inhibitor rapidly became undetectable after a single immunization. The one patient who failed to respond in this manner had very extensive disease and died within 2 weeks of the study. Repeated monthly immunization in the case of recurrent leiomyosarcoma was associated with the maintenance of the serum inhibitory activity at very low levels and with good clinical progress. The response to a single immunization is transient, the inhibitor becoming detectable again at 14-21 days. The possible role of circulating antigen in this serum inhibitory activity is discussed, as is the potential value of assaying the sera of cancer patients for serum inhibitory activity, as a means of monitoring the effects of treatment.