In vivo and in vitro effects of tumour specific antibodies with chlorambucil.

Abstract

Allo- and xenoantisera have been prepared against mouse tumours, and xenoantisera against human tumours, and absorbed to remove all antibodies against normal host lymphocytes as judged by cytotoxicity tests. The sera were fractionated and the Ig shown to be cytotoxic (complement mediated) for the appropriate tumour cells in vitro in the case of some mouse anti-mouse and rabbit anti-mouse, and specifically fluorescent in the case of goat anti-human tumour cells. In mouse model systems using lymphomata, these Ig preparations gave tumour specific protection. The protective effect of chlorambucil was also assessed in these models. Chlorambucil was linked to antibody and using the mouse theta system in vitro it could be seen that both antibody specificity and drug activity were retained in the complexes. Such drugged tumour specific antibodies were tested in vivo to find if the antibodies would carry the drug to the tumour target and destroy it, or so affect the immune balance as to change it in favour of the host. Favourable effects were found but these could not be attributed to “homing”. Protection against tumour death in the mouse lymphoma models was much better using complexes than could be achieved with either antibody or drug alone, but no better than the same amounts of antibody and drug injected unattached. Thus true homing has been shown in vitro but has not been achieved in vivo, though an additive or possibly a synergistic effect of antibody and drug has been demonstrated. It is likely that antibody destroys drug affected cells rather than the reverse.