Studies on the Mechanism of Immunological Enhancement of Tumor Homografts. 1. Specificity of Immunological Enhancement2

Abstract

This study of the specificity of immunological enhancement attempts to differentiate between the various hypotheses explaining the phenomenon of antibody-induced enhancement of tumor growth. Different mouse sarcomas were tested in systems designed to direct the antibodies against a number of antigenic components differentiating tumor and host, all belonging to the H-2 system. This was accomplished by variation of the specificity of the antiserum or the genotype of the recipients. All systems gave analogous results: a strong enhancing effect when the antibodies were directed against all tumor antigens foreign to the host, but no or diminished enhancement when only some of these antigens were covered by antibodies. Inhibition was directly related to the number or “strength” of the antigens remaining uncovered by antibodies. Passively transferred antibodies inhibited the humoral antibody response to tumor inoculation. Antibody action was specific in this system too: Passively transferred antibodies inhibited the immune response only against corresponding antigens, while other isoantigens on the same tumor cells still immunized efficiently. The pronounced specificity of the enhancing effect was incompatible with the hypotheses postulating antibody-induced alterations of tumor-cell characteristics, such as increased growth rate or increased resistance to the homograft reaction, but agreed with the assumption that antibodies interfere with the immunological relationship between tumor and host.