Use of trifunctional bispecific antibodies to prevent graft versus host disease induced by allogeneic lymphocytes.
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| Abstract |
A trifunctional bispecific antibody (BiLu) directed against murine CD3 and human epithelial-cell adhesion molecule (EpCAM) was tested for its ability to improve cell-mediated adoptive immunotherapy in a murine model of B16 melanoma cells transfected with human EpCAM. Intraperitoneal inoculation of naive C57BL/6 (C57) splenocytes induced lethal graft versus host disease (GVHD) in 85% to 97% of sublethally irradiated (BALB/c x C57BL/6) F1 (F1) hosts inoculated intraperitoneally with a sublethal or lethal dose of melanoma cells. BiLu antibodies given intraperitoneally concomitantly with alloreactive C57 cells effectively prevented GVHD-related and tumor-related death in 16 of 25 F1 mice inoculated with a sublethal tumor-cell dose and in 10 of 20 mice inoculated with a lethal tumor-cell dose over a follow-up period of more than 200 days. BiLu treatment also efficiently prevented severe GVHD, which was induced by high doses of BALB/c-derived splenocytes. Trifunctional bispecific antibodies (TbsAbs) capable of cross-linking T lymphocytes, natural killer, and other FcgammaR-positive effector cells, via their Fc region, to the tumor cells may be applied together with adoptive allogeneic-cell therapy to maximize antitumor responses while acting on GVHD in patients with minimal residual disease.
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| Authors | Shoshana Morecki, Horst Lindhofer, Elena Yacovlev, Yael Gelfand, Shimon Slavin |
| Journal | Blood (Blood) Vol. 107 Issue 4 Pg. 1564-9 (Feb 15 2006) ISSN: 0006-4971 [Print] United States |
| PMID | 16234351 (Publication Type: Journal Article) |
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