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Activation of Human Tumor-infiltrating Lymphocytes by Monoclonal Antibodies Directed to the CD3 Complex¹

Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115

We have used high concentrations of recombinant-methionyl human interleukin 2 (rIL-2) for the initial growth and expansion of human tumor-infiltrating lymphocytes (TIL). Early in the life of the TIL bulk culture, cytotoxicity was non-major histocompatibility complex restricted. Under these culture conditions antitumor cytotoxicity was observed to decline with increasing age of the bulk culture. In addition, TIL became refractory to rIL-2-induced expansion. We have used solid-phase anti-CD3 antibodies for TIL activation followed by culture in reduced concentrations of rIL-2 to reactivate TIL previously grown in high concentrations of rIL-2. TIL refractory to rIL-2 in terms of growth and antitumor cytotoxicity proved sensitive to anti-CD3 activation. The use of solid-phase anti-CD3 was also more effective than high concentrations of rIL-2 in the expansion of TIL when used at the start of culture. Finally, TIL could be induced to secrete IL-2 following solid-phase activation with anti-CD3. These data suggest that human TIL are susceptible to activation by signals directed at the CD3 complex of the TIL cell surface.

¹ This work was supported in part by NIH Grant CA-45484.

² Recipient of an American Cancer Society Career Development Award. To whom requests for reprints should be addressed, at Department of Surgery, Brigham & Woman's Hospital and Harvard Medical School, 75 Francis St., Boston, MA 02115.

Received 12/19/88. Revised 8/11/89. Accepted 11/ 7/89.

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