This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harel, W. Articles by Mitchell, M. S. Search for Related Content PubMed PubMed Citation Articles by Harel, W. Articles by Mitchell, M. S.

Increased Lysis of Melanoma by in Vivo-elicited Human Lymphokine-activated Killer Cells after Addition of Antiganglioside Antibodies in Vitro¹

Department of Medicine, University of Southern California School of Medicine and Comprehensive Cancer Center, Los Angeles, California 90033 [W. H., H. S., C. G. H., M. S. M.]; NeoRx Inc., Seattle, Washington 98119 [A. C. M.]; and Research Foundation of Scripps Clinic, La Jolla, California 92037 [R. A. R., D. A. C.]

Thirty-nine melanoma patients were treated with cyclophosphamide (350 mg/m²) followed 3 days later by 5 daily doses of interleukin 2 (3.6 million units/m² i.v.) weekly for 2 weeks. This cycle was repeated at least twice with a 1-week interval between cycles. Natural killer and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells were measured before treatment and on the last day of each cycle by chromium release assays. Development of LAK activity of >10 lytic units was correlated with a clinical response. There was no correlation between natural killer activity and clinical response. Antibody-dependent cell-mediated cytotoxicity of in vivo-induced LAK cells after the addition of mouse monoclonal antibodies (MAbs) in vitro was measured in 30 cases on the last day of each interleukin 2 cycle. Anti-G_D3 MAbs MB3.6, 11C64, 6H4, and R24 increased LAK cell cytotoxicity against G_D3-positive G_D2 melanoma cells while anti-G_D2 MAb 14.18 increased LAK cell cytotoxicity against G_D3-negative G_D2-positive melanoma cells. MAb 9.2.27 (IgG2a) directed against a chondroitin sulfate proteoglycan and its core protein with a molecular weight of 250,000 (p250) on human melanoma cells did not mediate antibody-dependent cell-mediated cytotoxicity. The effector cells in these antibody-dependent cell-mediated cytotoxicity reactions were Leu-19 positive. In preincubation experiments the MAbs showed superior binding to the melanoma target cells than to effector cells. Our results show that low dose interleukin 2 preceded by low dose cyclophosphamide effectively induces LAK cells in vivo. The cytotoxicity of these in vivo-activated LAK cells can be augmented in vitro by mouse MAbs against glycolipid antigens on the tumor.

¹ Supported by USPHS Grant RO1 CA-36233, a grant from the Concern Foundation, a contract from The Cetus Corporation, and gifts from Alan L. Gleitsman, the Morey and Claudia Mirkin Foundation, and Virginia L. Andleman. Presented in part at the 79th Annual Meeting of the American Association for Cancer Research, New Orleans, LA, May 25–28, 1988.

Received 6/15/89. Accepted 6/27/90.

This article has been cited by other articles:

				D. M. King, M. R. Albertini, H. Schalch, J. A. Hank, J. Gan, J. Surfus, D. Mahvi, J. H. Schiller, T. Warner, K. Kim, et al. Phase I Clinical Trial of the Immunocytokine EMD 273063 in Melanoma Patients J. Clin. Oncol., November 15, 2004; 22(22): 4463 - 4473. [Abstract] [Full Text] [PDF]

				F Mitjans, D Sander, J Adan, A Sutter, J. Martinez, C. Jaggle, J. Moyano, H. Kreysch, J Piulats, and S. Goodman An anti-alpha v-integrin antibody that blocks integrin function inhibits the development of a human melanoma in nude mice J. Cell Sci., January 8, 1995; 108(8): 2825 - 2838. [Abstract] [PDF]