Adoptive autoimmunotherapy. Cytotoxic effect of an autologous long-term T-cell line on malignant melanoma

Abstract

The in vitro and in vivo cytotoxic effects of an autologous long-term T-cell (LTTC) line were evaluated in a 65-year-old man with metastatic malignant melanoma. The patient's own T-cells were grown from a peripheral blood sample in a lymphocyte-conditioned medium. The cytotoxic effect of the LTTC against the patient's cultured melanoma cells was determined in vitro using the method of 51Cr release. Long-term T-cells produced specific lysis of 34% at an effector:target ratio of 30:1. Using allogeneic melanoma target cells, comparable or greater lysis was obtained in vitro. Long-term T-cells were injected into the infratumor and peritumor regions of two subcutaneous melanoma metastases of a lower extremity. A second injection of one of these lesions was followed 3 days later by an excisional tumor biopsy. Histologic examination showed many lymphocytes and necrotic areas in the injected lesions. Electron microscopic examination revealed numerous areas of lymphocyte-melanocyte membrane contact, membrane thickening, disintegration, hydropic cytoplasmic changes, and irreversible nuclear degenerative changes of melanocytes. Dividing lymphoblasts were also seen. These changes did not occur in noninjected tumor nodules. Long-term T-cell cultures yield immunologically functional cells capable of cytotoxic activity against allogeneic and autochthonous melanoma in vitro and against autochthonous melanoma in vivo. In vivo use after in vitro expansion of autologous immunocompetent cells (adoptive autoimmunotherapy) appears to be a feasible new approach to the study of human tumor immunology and treatment.