The Journal of Immunology, Vol 146, Issue 9 3250-3256, Copyright © 1991 by American Association of Immunologists

ARTICLES

Human peripheral blood lymphocytes targeted with bispecific antibodies release cytokines that are essential for inhibiting tumor growth

JH Qian, JA Titus, SM Andrew, D Mezzanzanica, MA Garrido, JR Wunderlich and DM Segal
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

We have compared the mechanisms by which human PBL targeted with bispecific antibodies either lyse tumor cells or block their growth in culture or in mice. We found that resting PBL were unable to mediate lysis, but were able to block tumor growth. Moreover, targeted PBL were unable to lyse bystander cells, whereas targeted PBL did block the growth of bystander tumor cells in culture and in nude mice. Supernatants from cultures of targeted PBL, or from PBL grown on anti- CD3-coated flasks, blocked the growth of tumor cells in the absence of added effector cells, and antibodies against TNF-alpha and IFN-gamma reversed the inhibition of tumor growth, but had no effect upon cytolysis mediated by targeted by PBL. Our results show that targeted human PBL mediate two different antitumor activities: lysis, which occurs rapidly and requires the direct attachment of the target cell to the cytotoxic cell, and tumor growth inhibition, which is mediated by cytokines released into the medium as a result of receptor cross- linking. The inhibition of bystander tumor growth in mice by targeted PBL suggests that factor release is sufficient to block tumor growth in vivo. Targeted factor release therefore provides a mechanism by which targeted PBL could block the growth of tumor cells in vivo that were not bound by the effector cells, but which were located in the vicinity of tumor cells that were bound.

This article has been cited by other articles:

				J. A. Rutigliano and B. S. Graham Prolonged Production of TNF-{alpha} Exacerbates Illness during Respiratory Syncytial Virus Infection J. Immunol., September 1, 2004; 173(5): 3408 - 3417. [Abstract] [Full Text] [PDF]

				I. Renard, D. Mezzanzanica, S. Canevari, S. Ferrini, J. Boniver, P. Delvenne, and N. Jacobs Anti-CD3/Anti-Epidermal Growth Factor Receptor-Bispecific Antibody Retargeting of Lymphocytes against Human Neoplastic Keratinocytes in an Autologous Organotypic Culture Model Am. J. Pathol., January 1, 2002; 160(1): 113 - 122. [Abstract] [Full Text] [PDF]

				P. Ruf and H. Lindhofer Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody Blood, October 15, 2001; 98(8): 2526 - 2534. [Abstract] [Full Text] [PDF]

				S. Bauer, C. Renner, J.-P. Juwana, G. Held, S. Ohnesorge, K. Gerlach, and M. Pfreundschuh Immunotherapy of Human Tumors with T-Cell-activating Bispecific Antibodies: Stimulation of Cytotoxic Pathways in Vivo Cancer Res., April 1, 1999; 59(8): 1961 - 1965. [Abstract] [Full Text] [PDF]