Observations on the Systemic Administration of Autologous Lymphokine-Activated Killer Cells and Recombinant Interleukin-2 to Patients with Metastatic Cancer

TLDR

The regimen was inspired by animal studies showing that systemic LAK cells plus interleukin‑2 can regress pulmonary and hepatic metastases in mice, though further clinical development is needed. The study aimed to evaluate the preliminary efficacy and safety of systemic autologous LAK cells combined with recombinant interleukin‑2 in patients with metastatic cancer. Twenty‑five patients with refractory metastatic cancer received 1.8–18.4 × 10¹⁰ autologous LAK cells generated from multiple leukaphereses and up to 90 doses of interleukin‑2. Objective tumor regression (>50 % volume) occurred in 11 of 25 patients, including one complete melanoma response lasting 10 months, while severe fluid retention—resolved after stopping interleukin‑2—was the main adverse effect.

Abstract

Abstract 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 18.4×1010 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.