Use of Tumor-Infiltrating Lymphocytes and Interleukin-2 in the Immunotherapy of Patients with Metastatic Melanoma

Lymphocytes extracted from freshly resected melanomas can be expanded in vitro and can often mediate specific lysis of autologous tumor cells but not allogeneic tumor or autologous normal cells. We treated 20 patients with metastatic melanoma by means of adoptive transfer of these tumor-infiltrating lymphocytes and interleukin-2, after the patients had received a single intravenous dose of cyclophosphamide. Objective regression of the cancer was observed in 9 of 15 patients (60 percent) who had not previously been treated with interleukin-2 and in 2 of 5 patients (40 percent) in whom previous therapy with interleukin-2 had failed. Regression of cancer occurred in the lungs, liver, bone, skin, and subcutaneous sites and lasted from 2 to more than 13 months. Toxic effects of interleukin-2 occurred, although the treatment course was short (five days); these side effects were reversible. It appears that in patients with metastatic melanoma, this experimental treatment regimen can produce higher response rates than those achieved with interleukin-2 administered alone or with lymphokine-activated killer cells. It is too early to determine whether this new form of immunotherapy can improve survival, but further trials seem warranted. WE have previously reported that adoptive immunotherapy using lymphokine-activated killer (LAK) cells plus interleukin-2 or high-dose interleukin-2 alone can result in the regression of cancer in a variety of murine models 1 2 3 4 and in selected patients with advanced metastatic cancer. 5 6 7 The LAK cells used in this therapy were non-T, non-B, "null" lymphocytes capable of recognizing and lysing a wide variety of fresh tumor cells but not normal target cells. 1 , 8 , 9 The ability of LAK cells to mediate tumor regression led us to search for other subpopulations of lymphocytes that might be effective in cancer treatment. We previously described a technique for the . . .