Studies on the Mechanism of Immunological Enhancement of Tumor Homografts. 11. Effect of Isoantibodies on Various Tumor Cells2

Abstract

Attempts were made to induce enhancement with tumors showing partial or full sensitivity to the cytotoxic action of H-2 antibodies. Partially sensitive tumors could be enhanced in H-2 systems. A completely sensitive leukemia could be enhanced in non-H-2 systems. Studies of hypotheses concerning immunological enhancement were performed. It could not be demonstrated that antibodies stimulated tumor growth. On the contrary inhibition was constant with several tumors and different test systems. Tumor cells exposed to antibodies for a short period in vitro, or a long time in vivo, did not change their transplantation characteristics to increased homotransplantability. Enhancement was obtained with tumor cells coated with antibodies in the absence of circulating antibodies in the hosts. Such antibody-coated cells were inferior to untreated cells in their ability to elicit the homograft reaction. It was concluded that antibodies did not change tumor-cell characteristics, such as growth rate or resistance to the homograft reaction, but probably exerted their effect by an "afferent" or "efferent" inhibition of transplantation immunity and not by a "central" mechanism. Different doses of antibodies affected various tumors differently Large doses caused inhibition with some tumors and enhancement with others, while smaller doses enhanced to various degrees. A possible explanation of the dose effect was advanced in terms of an "afferent" or "efferent" inhibition of the homograft reaction, and depended on the cytotoxic sensitivity of the tumor cells and their number of isoantigenic receptors.