We describe here the preliminary results of the systemic administration of autologous lymphokine-activated killer (LAK) cells and the recombinant-derived lymphokine interleukin-2 to patients with advanced cancer. This regimen was based on animal models in which the systemic administration of LAK cells plus interleukin-2 mediated the regression of established pulmonary and hepatic metastases from a variety of murine tumors in several strains of mice. We treated 25 patients with metastatic cancer in whom standard therapy had failed. Patients received both 1.8 to 18.4 X 10(10) autologous LAK cells, generated from lymphocytes obtained through multiple leukaphereses, and up to 90 doses of interleukin-2. Objective regression of cancer (more than 50 per cent of volume) was observed in 11 of the 25 patients: complete tumor regression occurred in one patient with metastatic melanoma and has been sustained for up to 10 months after therapy, and partial responses occurred in nine patients with pulmonary or hepatic metastases from melanoma, colon cancer, or renal-cell cancer and in one patient with a primary unresectable lung adenocarcinoma. Severe fluid retention was the major side effect of therapy, although all side effects resolved after interleukin-2 administration was stopped. Further development of this approach and additional patient follow-up are required before conclusions about its therapeutic value can be drawn.

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We have previously demonstrated (1-4) that the incubation of human peripheral blood lymphocytes or murine splenocytes in the lymphokine, interleukin 2 (IL-2) 1, leads to the generation of cells capable of lysing fresh syngeneic or autologous tumors in short-term chromium-release assays. These lytic cells have been termed lymphokine-activated killer (LAK) cells, and they exhibit broad lytic specificity for a variety of fresh tumors, but they do not lyse fresh normal cells. Recombinant IL-2 produced in E. coli and purified to apparent homogeneity is highly effective in generating LAK cells from both human and murine lymphocytes (5). We have recently demonstrated (6, 7) that the intravenous injection of LAK cells in conjunction with recombinant IL-2 can mediate the regression of established pulmonary metastases from a variety of sarcomas, as well as from the B 16 melanoma.Because recombinant IL-2 is capable of efficiently generating LAK cells in vitro, and because the systemic administration of LAK cells has potent antitumor activities, we have studied the possible use of high-dose recombinant IL-2 administered directly to tumor-bearing mice, aiming to generate LAK cells in vivo and mediate tumor regression. In these studies, we have shown that the systemic administration of high doses of recombinant IL-2 leads to the generation of LAK cells in the spleens of recipient mice and mediates the regression of established pulmonary metastases and subcutaneous implants from a variety of tumors. Tumor regression appears to be mediated by endogenously activated lymphocytes, presumably LAK cells, present at the tumor site and in the organs of mice receiving high-dose recombinant IL-2. Materials and MethodsAnimals. Female C57BL/6 mice were obtained from the Small Animal Section, Veterinary Resources Branch, National Cancer Institute, Bethesda, MD, or from The Jackson Laboratory, Bar Harbor, ME. All mice were 12-16 wk old when used in experiments.Tumors. The MCA-105 and MCA-106 tumors were induced in our laboratory by 1 Abbreviations used in this paper: HBSS, Hank's balanced salt solution; IL-2, interleukin 2; LAK, lymphokine-activated killer cells; NK, natural killer cells. J. ExP. MED.

These data add further weight to the conclusion that breast conservation using lumpectomy and breast irradiation is equivalent to mastectomy in terms of survival and ultimate local control for stage I and II breast cancer patients.