Skip to main content
PMC home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1987 Nov;25(3):231–241. doi: 10.1007/BF00199152

T cell recognition of a tumor-associated glycoprotein and its synthetic carbohydrate epitopes: stimulation of anticancer T cell immunity in vivo

Carina M Henningsson 1, Subnaicker Selvaraj 2, Grant D MacLean 3, Mavanur R Suresh 2,4, Antoine A Noujaim 2,4, B Michael Longenecker 1,4,✉
PMCID: PMC11038121  PMID: 2445486

Abstract

The Thomsen, Friedenreich (TF) and Tn carbohydrate antigens are expressed on the vast majority of human adenocarcinomas and are associated with aggressive behavior of certain tumors. TF and Tn antigens are also expressed on certain murine cancer cell lines including TA3-Ha, a highly lethal, transplantable mammary adenocarcinoma. TF and Tn cancer-associated carbohydrate haptens were synthesized, conjugated to protein carriers and used to demonstrate that delayed-type hypersensitivity (DTH) effector T cells can specifically recognize and respond to carbohydrate determinants on the TA3-Ha tumor-associated glycoprotein, epiglycanin. The effector cells were shown to have the helper DTH phenotype (Lytl+, Lyt2−, Thyl+) and it was demonstrated that they respond to specific carbohydrate determinants in an MHC-restricted fashion. These experiments provide the rationale for the use of synthetic tumor-associated glycoconjugates (S-TAGs) to stimulate anticancer T cell immunity. In support of this hypothesis, it was shown that preimmunization with the appropriate S-TAGs could provide a degree of protection against a subsequent tumor transplant and that antitumor effector Lytl+, Lyt2− T cells could be generated in vitro using the appropriate S-TAGs as antigens.

Keywords: Carbohydrate, Adenocarcinoma, Carbohydrate Antigen, Thyl, Cell Recognition

References

  • 1.Ashwell G, Morell AG. The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol. 1974;41:99. doi: 10.1002/9780470122860.ch3. [DOI] [PubMed] [Google Scholar]
  • 2.Bellamy A, Davidson AN, Feldmann M. Derivation of ganglioside-specific T cell lines of suppressor or helper phenotype from cerobrospinal fluid from multiple sclerosis patients. J Neuroimmunol. 1986;12:107. doi: 10.1016/0165-5728(86)90024-x. [DOI] [PubMed] [Google Scholar]
  • 3.Berzofsky JA, Cease KB, Berkower IJ, Marglait H, Cornette J, Delese C Immunodominance of amphipathic peptides and their localization on the cell surface for antigen presentation to helper T cells. In: Progress in immunology VI. Academic Press, New York (in press)
  • 4.Bhavanandan VP, Umemoto J, Banks JR, Davidson EA. Isolation and partial characterization of sialoglycopeptides produced by a murine melanoma. Biochemistry. 1977;16:4426. doi: 10.1021/bi00639a016. [DOI] [PubMed] [Google Scholar]
  • 5.Black PL, Vitetta ES, Forman J, Kang CY, May RD, Uhr JW. Role of glycosylation in the H-2 restricted cytolysis of virus-infected cells. Eur J Immunol. 1981;11:48. doi: 10.1002/eji.1830110111. [DOI] [PubMed] [Google Scholar]
  • 6.Bretscher PA. In vitro induction of delayed-type hypersensitivity. Eur J Immunol. 1979;9:311. doi: 10.1002/eji.1830090412. [DOI] [PubMed] [Google Scholar]
  • 7.Brondz BD, Snegirora AE, Rassulin YA, Shamborant OG. Modification of in vitro immune lymphocyte-target cell interaction by some biologically active drugs. Immunochemistry. 1973;10:175. doi: 10.1016/0019-2791(73)90006-2. [DOI] [PubMed] [Google Scholar]
  • 8.Chandrasekaran EV, Davidson EA. Sialoglycoproteins of human mammary cells: Partial characterization of sialoglycopeptides. Biochemistry. 1979;18:5615. doi: 10.1021/bi00592a015. [DOI] [PubMed] [Google Scholar]
  • 9.Codington JF, Linsley KB, Jeanloz RW. Immunochemical and chemical investigations of the structure of glycoprotein fragments obtained from epiglycanin, a glycoprotein at the surface of the TA3-Ha cancer cell. Carbohydr Res. 1975;40:171. doi: 10.1016/s0008-6215(00)82679-8. [DOI] [PubMed] [Google Scholar]
  • 10.Codington JF, Bhavanandan VP, Bloch KJ, Nikrui N, Ellard JV, Wang PS, Jeanloz RW. Antibody to epiglycanin and radioimmunoassay to detect epiglycanin-related glycoproteins in body fluids of cancer patients. J Natl Cancer Inst. 1984;73:1029. [PubMed] [Google Scholar]
  • 11.Damsky CH, Richa J, Solter D, Knudsen K, Buck CA. Identification and purification of a cell surface glycoprotein-mediated intercellular adhesion in embryonic and adult tissue. Cell. 1983;34:455. doi: 10.1016/0092-8674(83)90379-3. [DOI] [PubMed] [Google Scholar]
  • 12.Damsky CH, Knudsen KA, Buck CA. The biology of glycoproteins. New York: Plenum Press; 1984. Integral membrane glycoproteins in cell-cell and cell-substratum adhesion; p. 1. [Google Scholar]
  • 13.Drapkin MS, Appella E, Law LW. Immunogenic properties of a soluble tumor-specific transplantation antigen induced by simian virus 40. J Natl Cancer Inst. 1974;52:259. doi: 10.1093/jnci/52.1.259. [DOI] [PubMed] [Google Scholar]
  • 14.Economou GC, Takeichi N, Boone CW. Common tumor rejection antigens in methylcholanthrene-induced squamous cell carcinomas of mice detected by tumor protection and a radioisotopic footpad assay. Cancer Res. 1977;37:37. [PubMed] [Google Scholar]
  • 15.Feizi T. Demonstration by monoclonal antibodies that carbohydrate structures are glycoproteins and glycolipids are onco-developmental antigens. Nature. 1985;314:53. doi: 10.1038/314053a0. [DOI] [PubMed] [Google Scholar]
  • 16.Friberg S., Jr Comparison of an immunoresistant and an immunosusceptible ascities subline from murine tumor TA3. I. Transplantability, morphology and some physiocochemical characteristics. J Natl Cancer Inst. 1972;48:1463. [PubMed] [Google Scholar]
  • 17.Fujiwara H, Takai Y, Sakamoto K, Hamaoka T. The mechanism of tumor growth inhibition by tumor-specific Lyt 1+2− cells. I. Antitumor effect of Lyt 1+2− T cells depends on the existence of adherent cells. J Immunol. 1985;135:2187. [PubMed] [Google Scholar]
  • 18.Funakoshi I, Yamashina I. Structure of O-glycosidically linked sugar units from plasma membranes of an ascites hepatoma, AH 66. J Biol Chem. 1982;257:3782. [PubMed] [Google Scholar]
  • 19.Gately CL, Muul M, Greenwood MA, Papazoglou S, Dick SJ, Kornbrith DL, Smith BH, Gately MK. In vitro studies on the cell-mediated immune response to human brain tumors. II. Leukocyte-induced coats of gycosaminoglycan increases the resistance of glioma cells to cellular immune attack. J Immunol. 1984;133:3387. [PubMed] [Google Scholar]
  • 20.Gesner BM, Woodruff JJ. Cellular recognition. New York: Appleton-Country-Crafts, Inc.; 1969. Factors affecting the distribution of lymphocytes; p. 79. [Google Scholar]
  • 21.Goldstein SAN, Mescher MF. Carbohydrate moieties of major histocompatibility complex class I alloantigens are not required for their recognition by T lymphocytes. J Exp Med. 1985;162:1381. doi: 10.1084/jem.162.4.1381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Greenberg PD, Cheever MA, Fefer A. Cancer therapy. New York: Raven Press; 1982. Prerequisites for successful adoptive immunotherapy: Nature of effector cells and role of H-2 restriction; p. 31. [Google Scholar]
  • 23.Greene MI, Schatten S, Bromberg JS. Fundamental immunology. New York: Raven Press; 1984. Delayed hypersensitivity; p. 685. [Google Scholar]
  • 24.Hakomori SI, Kannagi R. Glycosphingolipids as tumor-associated and differentiation markers. J Natl Cancer Inst. 1983;71:231. [PubMed] [Google Scholar]
  • 25.Heidelberger M, Goebel WF, Avery OT. The soluble specific substances of a strain of Friedlanen's Bacillus. J Exp Med. 1925;42:701. doi: 10.1084/jem.42.5.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Hersey P. Review of melanoma antigens recognized by monoclonal antibodies (MAbs). Their functional significance and applications in diagnosis and treatment of melanoma. Pathology. 1985;17:346. doi: 10.3109/00313028509063778. [DOI] [PubMed] [Google Scholar]
  • 27.Houghton AN, Mintzer D, Cordon, Cardo C, Welt S, Fliegel B, Vadhan S, Carswell E, Melamed MR, Oettgen HF, Old LJ. Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: A phase I trial in patients with malignant melanoma. Proc Natl Acad Sci. 1985;82:1242. doi: 10.1073/pnas.82.4.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Irie RF, Tai T, Morton DL. Basic mechanisms and clinical treatment of tumor metastasis. New York: Academic Press; 1985. Antibodies to tumor-associated gangliosides (GM2, GD2): Potential for suppression of melanoma recurrence; p. 371. [Google Scholar]
  • 29.Kedar E, deCandazuri MO, Fahey JL. Enzymatic enhancement of cell-mediated cytotoxicity and antibody-dependent cell cytotoxicity. J Immunol. 1974;112:26. [PubMed] [Google Scholar]
  • 30.Koszinowski UH, Kramer M. Selective inhibition of T-suppressor-cell function by a monosaccharide. Nature. 1981;289:181. doi: 10.1038/289181a0. [DOI] [PubMed] [Google Scholar]
  • 31.Lemieux RU. Frontiers of chemistry. Oxford: Pergammon Press; 1983. The binding of carbohydrate structures with antibodies and lectins; p. 3. [Google Scholar]
  • 32.Lemieux RU, Bundle DR, Baker DA. The properties of a “synthetic” antigen related to the human blood group Lewisa . J Am Chem Soc. 1975;97:4076. doi: 10.1021/ja00847a035. [DOI] [PubMed] [Google Scholar]
  • 33.Longenecker BM, Rahman AFR, Barrington-Leigh J, Purser RA, Greenberg AH, Willans DJ, Keller O, Petrik PK, Thay TY, Suresh MR, Noujaim AA. Monoclonal antibody against a cryptic carbohydrate antigen of murine and human lymphocytes. I. Antigen expression in non-cryptic or unsubstituted form on certain murine lymphomas, on a spontaneous murine mammary carcinoma, and on several human adenocarcinomas. Int J Cancer. 1984;33:123. doi: 10.1002/ijc.2910330119. [DOI] [PubMed] [Google Scholar]
  • 34.Longenecker BM, Willians DJ, MacLean GD, Selvaraj S, Suresh MR, Noujaim AA. Monoclonal antibodies and synthetic tumor-associated glycoconjugates in the study of the expression of Thomsen-Friedenreich-like and Tn-like antigens on human cancers. J Natl Cancer Inst. 1987;78:489. [PubMed] [Google Scholar]
  • 35.MacDonald HR, Cerottini JC. Inhibition of T cell-mediated cytolysis by 2-deoxy-D-glucose: dissociation of the inhibitory effect from glycoprotein synthesis. Eur J Immunol. 1979;9:466. doi: 10.1002/eji.1830090610. [DOI] [PubMed] [Google Scholar]
  • 36.Miller JFAP, Vadas MA, Whitelaw A, Gamble J. H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice. Proc Natl Acad Sci. 1975;72:5095. doi: 10.1073/pnas.72.12.5095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Miller SC, Hay ED, Codington JF. Ultrastructural and histochemical differences in the cell surface properties of strain-specific and non-strain specific TA3 adenocarcinoma cells. J Cell Biol. 1977;72:511. doi: 10.1083/jcb.72.3.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Nelson M, Nelson DS. Thy and Ly markers on lymphocytes initiating tumor rejection. Cell Immunol. 1981;60:34. doi: 10.1016/0008-8749(81)90245-8. [DOI] [PubMed] [Google Scholar]
  • 39.Oppenheim JJ, Potter M. Cellular functions in immunity and inflammation. North Holland, New York, Amsterdam: Elsevier; 1981. Immunity and inflammation; p. 1. [Google Scholar]
  • 40.Paulsen H, Holck JP (1982) Synthese der Glycopeptide β-D-Gal(1→4)-α-D-G1cNAc(1→o)-L-Ser und β-D-Gal(1→4-α-D-GalNAc(1→o)-L-Thr. Liebigs Ann Chem 1121
  • 41.Perry LL, Greene MI. T cell subset interactions in the regulation of syngeneic tumor immunity. Fed Proc. 1981;40:39. [PubMed] [Google Scholar]
  • 42.Rahman FR, Longenecker BM. A monoclonal antibody specific for the Thomsen-Friedenreich cryptic T antigen. J Immunol. 1982;129:2021. [PubMed] [Google Scholar]
  • 43.Ratcliffe RM, Baker DA, Lemieux RU. Synthesis of the T [β-D-Gal-(1→3)-α-D-GalNAc]-antigenic determinant in a form useful for the preparation of an effective artificial antigen and the corresponding immunoadsorbent. Carbohydr Res. 1981;93:35. doi: 10.1016/s0008-6215(00)80750-8. [DOI] [PubMed] [Google Scholar]
  • 44.Rittenhouse HG, Manderino GL, Hass GM. Mucintype glycoproteins as tumor markers. Lab Med. 1985;16:556. [Google Scholar]
  • 45.Rosenthal AS, Shevach EM. Function of macrophages in antigen recognition by guinea pig T lymphocytes. J Exp Med. 1973;138:1194. doi: 10.1084/jem.138.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Roth S, McGuire EJ, Roseman S. Evidence for cell surface glycosyl transferases: Their potential role in cellular recognition. J Cell Biol. 1971;51:536. doi: 10.1083/jcb.51.2.536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Schmit A, Codington JF, Slayter HS. Epiglycanin as a membrane glycoprotein. Isolation of plasma membrane from the TA3-Ha tumor cell. Carbohydr Res. 1986;151:173. doi: 10.1016/s0008-6215(00)90338-0. [DOI] [PubMed] [Google Scholar]
  • 48.Sherblom AP, Buck RL, Carraway KL. Purification of the major sialoglycoproteins of 13762 MAT-B1 and MAT-C1 rat ascites mammary adenocarcinoma cells by density gradient centrifugation in cesium chloride and guanidine hydrochloride. J Biol Chem. 1980;255:783. [PubMed] [Google Scholar]
  • 49.Springer GF. T and Tn, general carcinoma autoantigens. Science. 1984;224:1198. doi: 10.1126/science.6729450. [DOI] [PubMed] [Google Scholar]
  • 50.Springer GF, Desai PR, Marthy MS, Tegetmeyer H, Seanlon EF. Human carcinoma-associated precursor antigens of the blood group MN system and the host's immune responses to them. Prog Allergy. 1979;26:42. [PubMed] [Google Scholar]
  • 51.Stellner K, Watanabe K, Hakomori S. Isolation and characterization of glycosphingolipids with blood group H specificity from membranes of human erythrocytes. Biochemistry. 1973;12:656. doi: 10.1021/bi00728a014. [DOI] [PubMed] [Google Scholar]
  • 52.Steplewski Z, Spira G, Blaszczyk M, Lubeck MD, Radbruch A, Illges H, Herlyn D, Rajewsky K, Scharff M. Isolation and characterization of antimonosialoganglioside monoclonal antibody 19-9 class-switch variants. Proc Natl Acad Sci. 1985;82:8653. doi: 10.1073/pnas.82.24.8653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Van den Eijden D, Evans NA, Codington JF, Reinhold V, Silber C, Jeanloz RW. Chemical structure of epiglycanin, the major glycoprotein of the TA3Ha ascites line. J Biol Chem. 1979;254:12153. [PubMed] [Google Scholar]
  • 54.Yogeeswaran G. Cell surface glycolipid and glycoproteins in malignant transformation. Adv Cancer Res. 1983;38:289. doi: 10.1016/s0065-230x(08)60191-8. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES