Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1965 Feb 28;121(3):439–462. doi: 10.1084/jem.121.3.439

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

Phil Gold 1, Samuel O Freedman 1
PMCID: PMC2137957  PMID: 14270243

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.

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ADLER F. L. Studies on the competition between antigens-implications for the allergist. N Y State J Med. 1960 Aug 1;60:2412–2416. [PubMed] [Google Scholar]
  2. AIZAWA M., SOUTHAM C. M. Serum antibodies following homotransplantation of human cancer cells. Ann N Y Acad Sci. 1960 May 31;87:293–307. doi: 10.1111/j.1749-6632.1960.tb23202.x. [DOI] [PubMed] [Google Scholar]
  3. BALE W. F., SPAR I. L., GOODLAND R. L. Experimental radiation therapy of tumors with I-131-carrying antibodies to fibrin. Cancer Res. 1960 Nov;20:1488–1494. [PubMed] [Google Scholar]
  4. BARRETT M. K. A critical analysis of tumor immunity. J Chronic Dis. 1958 Jul;8(1):136–157. doi: 10.1016/0021-9681(58)90045-6. [DOI] [PubMed] [Google Scholar]
  5. BILLINGHAM R. E., BRENT L., MEDAWAR P. B. Actively acquired tolerance of foreign cells. Nature. 1953 Oct 3;172(4379):603–606. doi: 10.1038/172603a0. [DOI] [PubMed] [Google Scholar]
  6. BJORKLUND B. Antigenicity of malignant and normal human tissues by gel diffusion techniques. Int Arch Allergy Appl Immunol. 1956;8(4):179–192. [PubMed] [Google Scholar]
  7. BJORKLUND B., BJORKLUND V. Antigenicity of pooled human malignant and normal tissues by cyto-immunological technique; presence of an insoluble, heat-labile tumor antigen. Int Arch Allergy Appl Immunol. 1957;10(3):153–184. [PubMed] [Google Scholar]
  8. BJORKLUND B., LUNDBLAD G., BJORKLUND V. Antigenicity of pooled human malignant and normal tissues by cyto-immunological technique. II. Nature of tumor antigen. Int Arch Allergy Appl Immunol. 1958;12(5):241–261. doi: 10.1159/000228458. [DOI] [PubMed] [Google Scholar]
  9. BOYDEN S. V. The immunological response to antigens of the tubercle bacillus; some experimental aspects. Prog Allergy. 1958;5:149–214. doi: 10.1159/000277644. [DOI] [PubMed] [Google Scholar]
  10. CINADER B. Acquired tolerance, autoantibodies and cancer. Can Med Assoc J. 1962 Jun 23;86:1161–1165. [PMC free article] [PubMed] [Google Scholar]
  11. COONS A. H., LEDUC E. H., CONNOLLY J. M. Studies on antibody production. I. A method for the histochemical demonstration of specific antibody and its application to a study of the hyperimmune rabbit. J Exp Med. 1955 Jul 1;102(1):49–60. doi: 10.1084/jem.102.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DEUTSCH H. F., MORTON J. I. Dissociation of human serum macroglobulins. Science. 1957 Mar 29;125(3248):600–601. doi: 10.1126/science.125.3248.600. [DOI] [PubMed] [Google Scholar]
  13. DEWEY W. C., BALE W. F., ROSE R. G., MARRACK D. Localization of antifibrin antibodies in human tumors. Acta Unio Int Contra Cancrum. 1963;19:185–196. [PubMed] [Google Scholar]
  14. GARB S., STEIN A. A. Production in rabbits of immune tolerance to a mixture of antigens. Proc Soc Exp Biol Med. 1962 Feb;109:305–308. doi: 10.3181/00379727-109-27186. [DOI] [PubMed] [Google Scholar]
  15. GARB S., STEIN A. A., SIMS G. The production of anti-human leukemic serum in rabbits. J Immunol. 1962 Feb;88:142–152. [PubMed] [Google Scholar]
  16. GOLDSTEIN G., SLIZYS I. S., CHASE M. W. Studies on fluorescent antibody staining. I. Non-specific fluorescence with fluorescein-coupled sheep anti-rabbit globulins. J Exp Med. 1961 Jul 1;114:89–110. doi: 10.1084/jem.114.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. HALPERN B. N., NEVEU T., SPECTOR S. On the nature of the chemical mediators involved in anaphylactic reactions in mice. Br J Pharmacol Chemother. 1963 Jun;20:389–398. doi: 10.1111/j.1476-5381.1963.tb01477.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. HAUSCHKA T. S. [Immunologic aspects of cancer: a review]. Cancer Res. 1952 Sep;12(9):615–633. [PubMed] [Google Scholar]
  19. HIRAMOTO R., BERNECKY J., JURANDOWSKI J., PRESSMAN D. Fibrin in human tumors. Cancer Res. 1960 Jun;20:592–593. [PubMed] [Google Scholar]
  20. KOBAYASHI K. Studies on the specific antigens of human gastric cancer. I. Tohoku J Exp Med. 1956 Feb 25;63(2-3):185–189. doi: 10.1620/tjem.63.185. [DOI] [PubMed] [Google Scholar]
  21. KOLDOVSKY P., SVOBODA J. On the question of the role of heterologous tolerance in possibility to immunize against tumour antigen. Folia Biol (Praha) 1962 Apr;8:101–104. [PubMed] [Google Scholar]
  22. LEVI E. PREPARATION OF AN ANTISERUM SPECIFIC TO A SPONTANEOUS MOUSE LEUKAEMIA AFTER THE INDUCTION OF ARTIFICIAL IMMUNOLOGICAL TOLERANCE TO NORMAL MOUSE TISSUE. Nature. 1963 Aug 3;199:501–502. doi: 10.1038/199501b0. [DOI] [PubMed] [Google Scholar]
  23. LEVI E., SCHECHTMAN A. M., SHERINS R. S., TOBIAS S. Tumour specificity and immunological suppression. Nature. 1959 Aug 15;184(Suppl 8):563–565. doi: 10.1038/184563a0. [DOI] [PubMed] [Google Scholar]
  24. LEVI E., SCHECHTMAN A. M. THE PREPARATION IN IMMUNOLOGICALLY TOLERANT RABBITS OF ANTISERA AGAINST THE EHRLICH ASCITES TUMOR. Cancer Res. 1963 Oct;23:1566–1570. [PubMed] [Google Scholar]
  25. MACBETH R. A., BEKESI J. G. TISSUE GLYCOPROTEINS IN RATS BEARING WALKER 256 CARCINOMA. Cancer Res. 1964 May;24:614–618. [PubMed] [Google Scholar]
  26. MITCHISON N. A. Immunological tolerance and immunological paralysis. Br Med Bull. 1961 May;17:102–106. doi: 10.1093/oxfordjournals.bmb.a069881. [DOI] [PubMed] [Google Scholar]
  27. OVARY Z. Passive cutaneous anaphylaxis in the mouse. J Immunol. 1958 Oct;81(4):355–357. [PubMed] [Google Scholar]
  28. PARAF A., FOUGEREAU M., METZGER J. J. [Study of spontaneous immunological reactivation]. C R Hebd Seances Acad Sci. 1963 Jul 1;257:312–314. [PubMed] [Google Scholar]
  29. RINDERKNECHT H. Ultra-rapid fluorescent labelling of proteins. Nature. 1962 Jan 13;193:167–168. doi: 10.1038/193167b0. [DOI] [PubMed] [Google Scholar]
  30. ROSE N. R., SHULMAN S., WITEBSKY E. Studies of normal and malignant tissue antigens. Cancer Res. 1956 Oct;16(9):831–841. [PubMed] [Google Scholar]
  31. SMITH R. T., BRIDGES R. A. Immunological unresponsiveness in rabbits produced by neonatal injection of defined antigens. J Exp Med. 1958 Aug 1;108(2):227–250. doi: 10.1084/jem.108.2.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. SOUTHAM C. M., MOORE A. E. Induced immunity to cancer cell homografts in man. Ann N Y Acad Sci. 1958 Oct 7;73(3):635–653. doi: 10.1111/j.1749-6632.1959.tb40840.x. [DOI] [PubMed] [Google Scholar]
  33. SOUTHAM C. M. Relationships of immunology to cancer: a review. Cancer Res. 1960 Apr;20:271–291. [PubMed] [Google Scholar]
  34. SPAR I. L., BALE W. F., GOODLAND R. L., DI CHIRO G. Preparation of purified I-131 labeled antisera to human fibrinogen. Preliminary studies in tumor patients. Acta Unio Int Contra Cancrum. 1963;19:197–200. [PubMed] [Google Scholar]
  35. TOOLAN H. W. Immunological responses elicited in the heterologous host by transplantable human tumors: use of the conditioned rat as a test medium. Ann N Y Acad Sci. 1957 Dec 16;69(4):830–841. doi: 10.1111/j.1749-6632.1957.tb49721.x. [DOI] [PubMed] [Google Scholar]
  36. Winzler R. J., Devor A. W., Mehl J. W., Smyth I. M. STUDIES ON THE MUCOPROTEINS OF HUMAN PLASMA. I. DETERMINATION AND ISOLATION. J Clin Invest. 1948 Sep;27(5):609–616. doi: 10.1172/JCI102006. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES