Large scale production of human lymphokine activated killer cells for use in adoptive immunotherapy |
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| Authors: | L M Muul E P Director C L Hyatt S A Rosenberg |
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| Institution: | 1. Kurita Animal Hospital, 139-1 Koga, Koga, Ibaraki, 306-0016, Japan;2. Division of Clinical Laboratory, Sanritsu Zelkova Veterinary Laboratory, 2-5-8 Kuji, Takatsu-ku, Kawasaki, Kanagawa, 213-0032, Japan;3. Murata Animal Hospital, 2016 Honnou, Mobara, Chiba, 299-4114, Japan;4. Laboratory of Infectious Diseases, Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan;1. Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan;2. Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China;3. Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China;4. AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan;5. SBI Pharmaceuticals Co., Ltd., Tokyo, Japan;1. Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, PR China;2. Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany;1. Department of Pulmonary Diseases, Vrije Universiteit University Medical Center, Institute for Cardiovascular Research, Amsterdam, The Netherlands;2. Institut National de la Santé et de la Recherche Unités Mixtes de Recherche_S 999, Pulmonary Hypertension: Pathophysiology and Novel Therapies, Hôpital Marie Lannelongue, Le Plessis-Robinson, Paris, France;3. Faculty of Medicine, Paris-South University, Kremlin-Bicêtre, Paris, France;4. National Reference Center of Pulmonary Hypertension, Department of Pulmonology and Intensive Care Unit for Respiratory Diseases, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Kremlin-Bicêtre, Paris, France;5. Department of Pathology, Hôpital Marie Lannelongue, Le Plessis-Robinson, Paris, France;6. Department of Thoracic and Vascular Surgery, Hôpital Marie Lannelongue, Le Plessis-Robinson, Paris, France;7. Department of Clinical Genetics, Hôpital Pitié-Salpêtrière, Assistance Publique–Hôpitaux de Paris and Unités Mixtes de Recherche_S 1166-ICAN, Institut National De La Santé Et De La Recherche Unités Mixtes De Recherche, Université Pierre et Marie Curie Sorbonne Universités, Paris, France;1. Key Laboratory of Zoonosis Research, Ministry of Education, The First Hospital, Jilin University, Xinmin street 71, Changchun, China;2. Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Xi’an Road 5333, Changchun, China;3. College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China;4. Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, China |
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| Abstract: | Immunotherapy utilizing the adoptive transfer of lymphokine activated killer (LAK) cells in conjunction with recombinant interleukin 2 (RIL-2) is capable of reducing established metastatic cancer in a variety of animal tumor models. A major difficulty in the application of these efforts to the treatment of human cancer has been the activation in vitro of up to 2 X 10(11) human peripheral blood lymphocytes obtained by repeated leukaphereses. We have thus developed optimal and simplified techniques for the generation of human LAK cells for use in clinical trials. We have found that 1.5 X 10(9) lymphocytes separated on Ficoll-Hypaque gradients and incubated in 1000 ml of culture medium in a 2.3 liter roller bottle with 1000-1500 U of RIL-2 per ml, generated LAK cells capable of killing fresh human tumor cells in a 4 h chromium release assay. The culture medium used was RPMI 1640 with 2 mM glutamine, 2% heat-inactivated human AB serum, 50 micrograms/ml streptomycin and gentamicin and 50 U/ml penicillin. This technique allows activation of sufficient numbers of cells in a research laboratory setting to conduct human clinical trials. The administration of LAK cells generated in this fashion can mediate the regression of human tumors when administered in conjunction with IL-2. |
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