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 Blood, 15 February 2006, Vol. 107, No. 4, pp. 1564-1569.
Prepublished online as a Blood First Edition Paper on October 18, 2005; DOI 10.1182/blood-2005-07-2738.

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NEOPLASIA

Use of trifunctional bispecific antibodies to prevent graft versus host disease induced by allogeneic lymphocytes

Shoshana Morecki, Horst Lindhofer, Elena Yacovlev, Yael Gelfand, and Shimon Slavin

From the Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Center, Hadassah University Hospital, Jerusalem, Israel; and TRION Research, Martinsried, Germany.

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 Fc{gamma}R-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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