Sera from Fischer 344 rats bearing a 13762A ascites mammary adenocarcinoma (MTA) blocked cell-mediated cytotoxicity (CMC) by spleen cells in vitro and enhanced tumor growth in vivo. Blocking (or enhancing) factors were detected in serum 3 days after i.p. immunization; peak activity occurred on days 5 and 7 and decreased sharply thereafter. Both CMC and the blocking of CMC were immunologically specific for mammary adenocarcinoma; normal breast cells did not inhibit lysis of tumor targets. Blocking factor in sera 3 and 5 days after immunization was present only in fractions coeluting with IgG on Sephadex G-200 chromatography. The blocking factors adsorbed to and quantitatively eluted from anti-rat IgG immunoadsorbant columns. In contrast, the Sephadex G-200 distribution of blocking factors of sera 7 and 10 days after immunization was polydisperse; although major activity was eluted in the IgG area, both void volume and lower m.w. areas also blocked CMC. The blocking activities of void volume and IgG fractions of all immune sera were removed by adsorption to immune lymphocytes but not by tumor cells, nonimmune lymphocytes, or lymphocytes immunized to unrelated antigens. Pretreatment of the cytolytic cells, but not the tumor cells, with the IgG fractions of immune sera inhibited CMC as well as if they had been continuously present in the assay. Collectively, these data suggest that blocking occurs at the level of the cytolytic lymphocyte, mediated either by tumor antigen-antibody to tumor antigen complexes, anti-receptor site antibodies, or both.
This work was supported by Contract NO1-CB-33905 from the National Institutes of Health.