DEMONSTRATION OF TUMOR-SPECIFIC ANTIGENS IN HUMAN COLONIC CARCINOMATA BY IMMUNOLOGICAL TOLERANCE AND ABSORPTION TECHNIQUES

TLDR

It remains unclear whether the additional antigens identified are qualitatively distinct from normal tissue antigens or simply present at higher concentrations in tumors. The authors generated antisera by (a) immunizing rabbits with pooled colon carcinoma extracts and absorbing the resulting antitumor antisera with normal colon and blood components, and (b) inducing immunological tolerance to normal colon in newborn rabbits before adult immunization with tumor material; the antisera were then characterized by agar gel diffusion, immunoelectrophoresis, hemagglutination, PCA, and immunofluorescence. The antisera exhibited distinct antibody activity against at least two tumor‑specific antigens common to both methods and two additional antigens exclusive to the tolerance technique, with no reactivity to bacterial contaminants or fibrin, demonstrating that colon carcinomas contain antigens absent from normal colonic tissue and present in multiple patients.

Abstract

Two methods were used to demonstrate the presence of tumor-specific antigens in adenocarcinomata of the human colon: (a) rabbits were immunized with extracts of pooled colonic carcinomata, and the antitumor antisera thus produced were absorbed with a pooled extract of normal human colon and with human blood components; (b) newborn rabbits were made immunologically tolerant to normal colonic tissue at birth, and were then immunized with pooled tumor material in adult life. Normal and tumor tissues were obtained from the same human donors in order to avoid misinterpretation of results due to individual-specific antigenic differences. The antisera prepared by both methods were tested against normal and tumor antigens by the techniques of agar gel diffusion, immunoelectrophoresis, hemagglutination, PCA, and immunofluorescence. Distinct antibody activity directed against at least two qualitatively tumor-specific antigens, or antigenic determinants, was detected in the antisera prepared by both methods and at least two additional tumor antigens were detected exclusively in antisera prepared by the tolerance technique. Whether these additional antigens were qualitatively different from normal tissue antigens, or merely present in tumor tissue in higher concentrations than in normal tissue has not as yet been determined. Furthermore, it was shown that the tumor-specific antibodies were not directed against bacterial contaminants or against the unusually high concentrations of fibrin found in many neoplastic tissues. It was concluded from these results that the pooled tumor extracts contained tumor-specific antigens not present in normal colonic tissue. Identical tumor-specific antigens were also demonstrated in a number of individual colonic carcinomata obtained from different human donors.