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KMID : 0391319910010010074
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Korean Journal of Biological Response Modifiers
1991 Volume.1 No. 1 p.74 ~ p.83
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Adoptive Immunotherapy of Human Cancer with Lymphokine-Activated Killer Cells and Interleukin-2
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Choi Yong-Mook
Choeh Kyuchul
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Abstract
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Interleukin-2(IL-2) is a lymphokine which has various immunomodulatory effects. The administration of IL-2 can mediate enhancement of cellular immune responses, induction of lymphocyte proliferation, production of cytokines, and regression of established tumors in animal medels. In clinical fields, this cytokine has significant dose and schedule dependence with regard to both clinical toxicity and biological activity. This article reviews our experiences and the other current status of clinical trials with IL-2 used as a single agent in variety of doses and schedules or in combination with lymphokine-activated killer (LAK) cells. The article also discusses the rationale, preclinical studies, and preliminary experience with IL-2 in combination with other cytokines such as interferon and tumor infilitrating lymphocytes (TIL), and other anticancer modalities such as surgery, radiotherapy and chemotherapy.
The effects of adoptive immunotherapy with LAK cells &/or IL-2 were evaluated in 18 patients with advanced cancer for whom standard therapy had proved ineffective. Six patients were treated with LAK cells only, 4 patients treated with continuous IV infusion of IL-2 alone, and 8 patients treated with LAK cells plus IL-2. In a patient with hepatoma LAK cells & IL-2 were infused by selective catheterization to a branch of hepatic artery, in a patient with gastric cancer complicated by cancer peritonitis LAK cells & IL-2 were infused to peritoneal cavity, and in a patient with renal cell carcinoma HLA-matched allogeneic LAK cells from 2 siblings were infused intravenously (8 times, total 2.49X 1010 cells). In the atient with gastric cancer who was treated by peritoneal infusion, LAK cells were induced from mononuclear cells obtained from ascites.
Of 17 evaluable patients, 1 (5.9%) had complete response(CR), 1 (5.9%) had partial response (PR), 4(23.5%) had minimal response(Min R), and 2 (11.8%) had mixed responses(Mix R). Especially, of 7 evaluable patients treated with LAK cells plus IL-2, 1 (14.3 %) had CR, 1 (14.3 % ) had PR, and 3 (42.9%) had Min R. CR with relapse-free survival for 19 months was observed in a lung cancer(squamous cell carcinoma). PR was observed in a lung cancer, and Min R were observed in 2 hepatomas, 1 gastric cancer & 1 neuroblastoma. In 3 pediatric patients (3 to 7 years old) continuous infusion of IL-2 in dose-escalation mode were studied. They were able to tolerate 4,000,OOOKH u/M2/day for of IL-2(1KH u=1.1 BRMP u). Most of adult patients well tolerated 2,000,000KH u/M2/day for 5days of IL-2 in mode of continuous IV infusion.
Most common side effects were chills and fever which chould be prevented or minimized by premedication of antihistamine, indomethacin and acetaminophen, and IV infusion of demerol. Serious side effects were complicated by capillary leak syndrome which showed hypotension, generalized edema, weight gain, pulmonary edema, dyspnea, azotemia and mental change. And anemia, thrombocytopenia, lymphopenia and eosinophilia were also noticed. Future efforts are aimed at increasing the antitumor efficacy and decreasing the toxicity of IL-2 administration.
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KEYWORD
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