Intralesional injection of interleukin-2-expanded autologous lymphocytes in melanoma and breast cancer patients: a pilot study.
The clinical effect of intralesional injection of interleukin-2 (IL-2)-cultured autologous lymphocytes was assessed in seven patients with cutaneous, recurrent tumor nodules (12 melanoma and 8 mammary cancer lesions). Each tumor nodule was injected 3-10 times, once weekly, with IL-2-cultured lymphoid cells (CLC), 40-400 million cells at each injection. Lymphoid cells obtained from buffy coats were separated on Ficoll-Paque, cryopreserved in liquid nitrogen, thawed, and cultured for 1-2 weeks in the presence of crude IL-2 (containing phytohemagglutinin) before injection. CLC were tested for sterility, percent E-rosette-forming cells, and cytotoxicity against K562, allogeneic melanoma, and breast cancer cell lines and autologous tumor cells. Enhanced cytotoxicity was expressed by IL-2 CLC, as compared with nonstimulated peripheral blood lymphocytes (PBL). Arrest of tumor growth (compared with untreated lesions) was observed in eight lesions and partial regression in three lesions. Moreover, complete regression was noted in one large melanoma lesion treated with low-dose irradiation prior to intralesional administration of CLC and in three small intracutaneous melanoma lesions treated with CLC only. Histopathological findings of responding lesions showed infiltration with lymphoid cells and macrophages, with the tumor cells sparsely dispersed. No untoward side effects of CLC injections were observed. The present study points to the feasibility of trials of adoptive immunotherapy in cancer patients as indicated by the following: (a) response of lymphoid cells to IL-2 adequate--although reduced--in patients with metastatic disease, including those after chemo- or radiotherapy; (b) possibility of cryopreservation of PBL and repeated culturing in IL-2 after thawing, with cytotoxic activity unimpaired; (c) demonstrably enhanced cytotoxicity in vitro of IL-2 CLC; (d) demonstrable--although limited--clinical response to in situ treatments with IL-2 CLC; (e) good tolerance of treatment with CLC.
D001943:Breast Neoplasms / Q000628:therapy*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007167:Immunotherapy; D007376:Interleukin-2 / Q000276:immunology*; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000628:therapy*; D010865:Pilot Projects; D014182:Transplantation, Autologous
D007376:Interleukin-2