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-Interferon Enhances Spontaneous and Bispecific Anti-CD3 x Antitumor Antibody-directed Lymphokine-activated Killer Cell Cytotoxicity
Fourth Department of Internal Medicine, Nippon Medical School [A. A., H. N.], 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113, and Department of Immunology, Juntendo University School of Medicine [A. A., H. Y., H. M., K. O.], 3-1-3 Hongo, Bunkyo-ku, Tokyo 113, Japan
The interaction between LFA-1 and its natural ligand, ICAM-1, plays an important role in leukocyte adhesion and signal transduction. LFA-1-mediated T-cell adhesion is generally activated by CD3-mediated signal in association with T-cell receptor-mediated recognition of the antigen/major histocompatibility complex on antigen-presenting cells. In the present study, we compared spontaneous or bispecific antibody (BsAb)-directed LAK cell cytotoxicity against ICAM-1+ or ICAM-1- small cell lung cancer (SCLC) cell lines.
-Interferon (IFN-
)-induced ICAM-1 expression on ICAM-1- SCLC cell lines, and susceptibility to LAK cells was increased simultaneously. Increased cytolysis of the IFN-
-treated SCLC was inhibited by an anti-ICAM-1 monoclonal antibody (mAb). Furthermore, LAK cell cytotoxicity directed by BsAb, which was composed of OKT3 and anti-SCLC mAb, was also increased by the IFN-
treatment of SCLC, and this increase was inhibited by an anti-ICAM-1 mAb but not by anti-Class I or anti-CD2 mAb. These results suggest that a prior administration of IFN-
would enhance the efficacy of the following specific targeting therapy utilizing BsAb and LAK cells by up-regulating the ICAM-1 expression on tumor target cells. The combinational use of IFN-
and anti-CD3 x anti-tumor BsAb might be a promising way of enhancing LAK cell-mediated adoptive immunotherapy in small cell lung cancer patients.
1 to whom requests for reprints should be addressed, at 4th Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113, Japan.
Received 10/30/91. Accepted 7/ 7/92.
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