title: Targeting human T-lymphocytes with bispecific antibodies to react against human ovarian carcinoma cells growing in nu/nu mice.
abstract: 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.
authors: Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
authors: M A
authors: MA
authors: Garrido
authors: M J
authors: MJ
authors: Valdayo
authors: D F
authors: DF
authors: Winkler
authors: J A
authors: JA
authors: Titus
authors: T T
authors: TT
authors: Hecht
authors: P
authors: P
authors: Perez
authors: D M
authors: DM
authors: Segal
authors: J R
authors: JR
authors: Wunderlich
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins