This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Garrido, M. A. Articles by Wunderlich, J. R. Search for Related Content PubMed PubMed Citation Articles by Garrido, M. A. Articles by Wunderlich, J. R.

Targeting Human T-Lymphocytes with Bispecific Antibodies to React against Human Ovarian Carcinoma Cells Growing in nu/nu Mice

Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892 [M. A. G., M. J. V., D. F. W., J. A. T., P. P., D. M. S., J. R. W.], and University of Maryland Baltimore County, Department of Biological Sciences, Catonsville, Maryland 21228 [T. T. H.]

In the present study we tested whether human T-cells from normal donors can be targeted against human ovarian carcinoma cells and block i.p. growth of an established tumor in immunodeficient mice. For targeting we used chemically cross-linked bispecific monoclonal antibodies (mAbs) reacting with CD3 on the T-cells and with cell-surface antigens selectively expressed by tumor cells. The tumor model consisted of mice given i.p. injections of a human ovarian carcinoma cell line, OVCAR-3, whose growth includes development of massive ascites. Peripheral blood lymphocytes from normal human donors were cultured overnight with 50–100 units/ml recombinant interleukin 2, coated with bispecific antibodies, and injected i.p. into mice 4–6 days after tumor inoculation, at which time tumor cells were established and growing in about 85% of the hosts. Tumor growth was assessed by the number of tumor cells, and in some tests by cell-free tumor antigen, recovered in peritoneal lavage fluid collected 15 days after tumor priming. Treatment with lymphocytes retargeted with bispecific mAbs, prepared with anti-CD3 and three different antitumor mAbs, 113F1, OVB-3, and MOv19, gave highly significant increases in percentages of mice without detectable tumor. Controls showed that the antitumor activity of retargeted lymphocytes did not result simply from antibody-dependent cellular cytotoxicity or from heteroconjugates reacting only with CD3 or with lymphocyte major histocompatibility complex determinants and tumor cells. These results show that targeted T-lymphocytes can significantly decrease the growth of an established tumor in a fashion specific for antigens expressed by the neoplastic cells.

Received 11/13/89. Revised 3/ 9/90.

This article has been cited by other articles:

				T. Waldmann Monoclonal antibodies in diagnosis and therapy Science, June 21, 1991; 252(5013): 1657 - 1662. [Abstract] [PDF]