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

TLDR

Lymphocytes isolated from melanoma can be expanded in vitro to specifically lyse autologous tumor cells, and although early data are inconclusive, further trials are warranted. We treated 20 metastatic melanoma patients with adoptive transfer of tumor‑infiltrating lymphocytes plus interleukin‑2 after a single dose of cyclophosphamide. The regimen produced objective regression in 60 % of IL‑2 naïve patients and 40 % of IL‑2 pre‑treated patients, with durable responses in multiple organs lasting up to 13 months, reversible IL‑2 toxicity, and higher response rates than IL‑2 alone or with lymphokine‑activated killer cells.

Abstract

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.