Clinical Cancer Research, Vol 4, Issue 3 721-730, Copyright © 1998 by American Association for Cancer Research

ARTICLES

Bispecific antibodies increase T-cell stimulatory capacity in vitro of human autologous virus-modified tumor vaccine

C Haas, G Strauss, G Moldenhauer, RM Iorio and V Schirrmacher
Division of Cellular Immunology, German Cancer Research Center, Heidelberg.

The production and functional testing of two new bispecific (bs) hybrid antibodies [Abs; bs Ab hemagglutinin-neuraminidase (HN) x CD3 and bs Ab HN x CD28] designed for cancer vaccine modification are described. They allow distinct modifications of the human tumor cell vaccine ATV-NDV, an autologous tumor cell vaccine already modified by infection with Newcastle disease virus. The bs Abs use the viral HN molecule as a common foreign anchoring molecule for attachment to the tumor cells and allow the introduction of anti-CD3 or anti-CD28 T-cell-stimulatory molecules. The bs Abs attached to tumor target cells were able to cross-link CTL effector cells and up-regulate T-cell activation markers on autologous cancer patient-derived CD4 and CD8 T lymphocytes. This strategy of combining a cellular vaccine with a bs Ab is highly specific, quick, and economical and has broad-range applications. Five ng or less of target cell-bound bs Ab HN x CD28 were effective at augmenting T-cell-mediated antitumor cytotoxicity.

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