TUMOR TARGETING OF THE ANTIOVARIAN CARCINOMA X ANTI-CD3 TCR BISPESIFIC MONOCLONAL-ANTIBODY OC/TR AND ITS PARENTAL MOV18 ANTIBODY IN EXPERIMENTAL OVARIAN-CANCER/

The anti-tumour x anti-T-cell bispecific monoclonal antibody (biMAb) O C/TR is a biologically produced biMAb combining the anti-ovarian carci noma activity of the MOv18 MAb with anti-CD3/T-cell receptor (TCR) com plex activity. In this study, the in vitro binding characteristics of the OC/TR biMAb and its tumour targetting potential in nude mice with Hela tumours was studied. Scatchard analysis revealed that the affinit y constant of the biMAb was 7 times lower than the affinity of the par ental MOv18 antibody. Uptake of the OC/TR antibody in the Hela xenogra fts in nude mice was significantly higher than the tumour uptake of an irrelevant control antibody, indicating that the radioiodinated OC/TR biMAb specifically localized in the tumour xenografts. However, tumou r uptake was significantly lower than the tumour uptake of the parenta l MOv18 antibody. This reduced tumour uptake most likely is a result o f its reduced affinity. We conclude that, despite the loss of bivalent tumour cell binding, the biMAb OC/TR can still specifically localize in tumours. This indicates that the first prerequisite of an effective therapeutic approach using systemically applied biMAb can be met. Whe ther the interaction with human T-cells will affect the tumour targeti ng potential of the biMAb in patients remains to be investigated.