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Membrane-Bound Anti-CD3 Monoclonal Antibodies Trigger Cytolytic T-lymphocyte—Mediated Tumor Lysis
Steven J. Mentzer, MD;
Richard E. Wilson, MD;
Steven J. Burakoff, MD;
Steven H. Herrmann, PhD
Arch Surg. 1988;123(10):1280-1285.
Abstract
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• Cytolytic T lymphocytes (CTLs) are an efficient immune mechanism for the destruction of foreign or pathogenic cells. Attempts to use CTLs in human cancer therapy have focused on the cell-surface molecules that regulate CTL function. An important molecule in CTL function is the CD3 antigen. Biochemical characterization has suggested that the CD3 antigen may function as a "trigger" for T-lymphocyte activation. To investigate this possibility, we used monoclonal antibody (MAb) to the CD3 antigen to trigger activation of long-term CTL lines. The anti-CD3 MAb was able to trigger killing of a variety of human and mouse tumor cell lines; however, not all tumor cells were lysed by the CTL. The susceptibility of the tumor cells to CTL-mediated lysis appeared to correlate with the binding of the anti-CD3 MAb to the tumor cell surface. The requirement for surface binding of the MAb was tested by covalently cross-linking the anti-CD3 MAb to the tumor cell membrane. Membrane-bound anti-CD3 MAb triggered high levels of CTL-mediated tumor cell killing. Similar results were obtained when anti-CD3 MAb was cross-linked to phosphatidylethanolamine and inserted into the cell membrane. These results indicate that the attachment of anti-CD3 MAb to the tumor cell surface provides a powerful new approach to the in vitro activation of human killer T cells and the in vivo treatment of human cancer.
(Arch Surg 1988;123:1280-1285)
Author Affiliations
From the Department of Surgery, Brigham and Women's Hospital (Drs Mentzer and Wilson), and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School (Drs Burakoff and Herrmann), Boston.
Footnotes
Accepted for publication July 14, 1987.
Read before the Annual Meeting of the Society of Surgical Oncology, London, May 7, 1987.
Reprint requests to 1630D, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115 (Dr Mentzer).
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