BISPECIFIC ANTIBODIES INCREASE T-CELL STIMULATORY CAPACITY IN-VITRO OF HUMAN AUTOLOGOUS VIRUS-MODIFIED TUMOR VACCINE

The production and functional testing of two new bispecific (bs) hybri d 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 w ith Newcastle disease virus, The bs Abs use the viral HN molecule as a common foreign anchoring molecule for attachment to the tumor cells a nd allow the introduction of anti-CD3 or anti-CD28 T-cell-stimulatory molecules. The bs Abs attached to tumor target cells were able to cros s-link CTL effector cells and up-regulate T-cell activation markers on autologous cancer patient-derived CD4 and CD8 T lymphocytes, This str ategy of combining a cellular vaccine with a bs Ab is highly specific, quick, and economical and has broad-range applications, Five ng or le ss of target cell-bound bs Ab HN x CD28 were effective at augmenting T -cell-mediated antitumor cytotoxicity.