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

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 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.

Immunology and immunotherapy approaches for prostate cancer

“…1 However, the first apparent indication that metastatic human cancers could be eliminated using immunological manipulations came from studies of the administration of autologous lymphokine-activated killer cells and interleukin 2 (IL-2) to patients with metastatic melanoma, colon cancer or renal-cell cancer. 2 Following a considerable debate as to whether the immune system can recognize and eliminate tumour cells, recent evidence suggests that immune cells can protect against the development of tumours. 3,4 Nevertheless, the majority of the progress in tumour immunology has been made in the more immunogenic tumours such as melanoma, lymphoma and renal cell carcinoma, whereas a limited success has been achieved with all other less immunogenic cancers.…”

High Dose IL‐2‐Activated Murine Natural Killer (A‐NK) Cells Accumulate Glycogen and Granules, Lose Cytotoxicity, and Alter Target Cell Interaction In Vitro

“…There are numerous clinical attempts based on adoptive immunotherapy (AIT) of cancer disease with various subsets of LAK cells [5][6][7][8][9]. Particular interest has been directed to those LAK cells that grow adherent to the culture plastic and exhibit an enhanced antitumour cell effect [9,10].…”

Safety and efficacy of subcutaneous and continuous intravenous infusion rIL-2 in patients with metastatic renal cell carcinoma

“…In initial studies by Rosenberg and coworkers at the National Cancer Institute in the United States, rIL-2 was administered as high-dose intravenous bolus (i.v.b.) injection (Rosenberg et al, 1985). A typical i.v.b.…”