In conclusion
Carbohydrate antigens are the most abundant antigens expressed at the cancer cell surface and have been shown to be uniquely effective targets for immune recognition and attack. The basis for cancer vaccines that primarily induce an antibody response, such as vaccines against these carbohydrate antigens, is now well established in both experimental models and the clinical setting. In both cases, antibody administration or induction has been especially effective in the adjuvant setting when the targets are circulating tumor cells and micrometastases. The patterns of carbohydrate antigens expressed by different tumor types has been established, paving the way for polyvalent-antibody-inducing vaccines. This then forms the rationale for the construction and testing of carbohydrate vaccines against cancer, the focus of the second part of this review.
Keywords: Melanoma, Circulate Tumor Cell, Conjugate Vaccine, Carbohydrate Antigen, Polysialic Acid
References
- 1.Livingston PO, Oettgen HF, Old LJ. Immunological aspects of cancer therapeutics. New York: Wiley; 1982. Specific active immunotherapy in cancer therapy; pp. 363–404. [Google Scholar]
- 2.Livingston PO. Active specific immunotherapy in the treatment of cancer. In: Oettgen HF, editor. Immunology and allergy clinics of north America. Human cancer immunology. II, vol 11. London: Saunders; 1991. pp. 402–423. [Google Scholar]
- 3.Brystryn JC, Ferrone S, Livingston PO (1993) Specific immunotherapy of cancer with vaccines. Ann NY Acad Sci 690
- 4.Livingston P. Approaches to augmenting the immunogenicity of melanoma gangliosides: from whole melanoma cells to ganglioside-KLH conjugate vaccines. Immunol Rev. 1995;145:147–166. doi: 10.1111/j.1600-065X.1995.tb00080.x. [DOI] [PubMed] [Google Scholar]
- 5.Old LJ. Cancer immunology: the search for specificity. G. H. A. Clowes Memorial Lecture. Cancer Res. 1981;41:361–375. [PubMed] [Google Scholar]
- 6.AAP Universal hepatitis B immunization. Pediatrics. 1992;89:795–800. [PubMed] [Google Scholar]
- 7.Fishbein DB, Robinson LE. Rabies. N Engl J Med. 1993;329:1632–1638. doi: 10.1056/NEJM199311253292208. [DOI] [PubMed] [Google Scholar]
- 8.Srivastava PK, Old LJ. Individually distinct transplantation antigens of chemically induced mouse tumors. Immunol Today. 1988;9:78–78. doi: 10.1016/0167-5699(88)91269-8. [DOI] [PubMed] [Google Scholar]
- 9.Rohrer JW, Rohrer SD, Barsoum A, Coggin JH. Differential recognition of murine tumor-associated oncofetal transplantation antigen and individually specific transplantation antigens by syngeneic cloned BALB/c and RFM mouse T cells. J Immunol. 1994;152:754–754. [PubMed] [Google Scholar]
- 10.Wilson RE, Hager EB, Hampers CI, et al. Immunologic rejection of human cancer transplanted with a renal allograft. N Engl J Med. 1968;278:479–479. doi: 10.1056/NEJM196802292780904. [DOI] [PubMed] [Google Scholar]
- 11.Zukoski CF, Killen DA, Ginn E, et al. Transplanted carcinoma in immunosuppressed patients. Transplantation. 1970;9:71–71. doi: 10.1097/00007890-197001000-00021. [DOI] [PubMed] [Google Scholar]
- 12.Jones PC, Sze LL, Liu PY, Morton DL, Irie RF. Prolonged survival for melanoma patients with elevated IgM antibody to oncofetal antigen. J Natl Cancer Inst. 1981;66:249–254. [PubMed] [Google Scholar]
- 13.Livingston PO, Ritter G, Srivastava P, Padavan M, Calves MJ, Oettgen HF, Old LJ. Characterization of IgG and IgM antibodies induced in melanoma patients by immunization with purified GM2 ganglioside. Cancer Res. 1989;49:7045–7050. [PubMed] [Google Scholar]
- 14.Kawakami Y, Eliyahu S, Jennings C, Sakaguchi K, Kang X, Southwood S, Robbins PF, Sette A, Appella E, Rosenberg SA. Recognition of multiple epitopes in the human melanoma antigen gpl00 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression. J Immunol. 1995;154:3961–3968. [PubMed] [Google Scholar]
- 15.Livingston PO (1997) The case for melanoma vaccines that induce antibodies. In: Kirkwood JM (ed) Molecular diagnosis, prevention and treatment of melanoma.(in press)
- 16.Darnell RB. Onconeural antigens and the paraneoplastic neurologic disorders: At the intersection of cancer, immunity, and the brain. Proc Natl Acad Sci USA. 1996;93:4529–4536. doi: 10.1073/pnas.93.10.4529. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Dalmau J, Graus F, Cheung N-K V, Rosenblum MK, Ho A, Canete A, Delattre J-Y, Thompson SJ, Posner JB. Major histocompatibility proteins, anti-Hu antibodies, and paraneoplastic encephalomyelitis in neuroblastoma and small cell lung cancer. Cancer. 1995;75:99–109. doi: 10.1002/1097-0142(19950101)75:1<99::AID-CNCR2820750117>3.0.CO;2-I. [DOI] [PubMed] [Google Scholar]
- 18.Livingston PO, Wong GY, Adluri S, Tao Y, Padavan M, Parente R, Hanlon C, Calves MJ, Helling F, Ritter G. Improved survival in stage II melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol. 1994;12:1036–1044. doi: 10.1200/JCO.1994.12.5.1036. [DOI] [PubMed] [Google Scholar]
- 19.Winter SF, Sekido Y, Minna JD, McIntire D, Johnson BE, Gazdar AF, Carbone DP. Antibodies against autologous tumor cell proteins in patients with small-cell lung cancer: Association with improved survival. J Natl Cancer Inst. 1993;85:2012–2018. doi: 10.1093/jnci/85.24.2012. [DOI] [PubMed] [Google Scholar]
- 20.Riethmuller G, Schneider-Gadicke E, Schlimok G, Schmiegel W, Raab R, Hoffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R, Buggisch P, Witte J, The German Cancer Aid 17-1A Study Group Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes’ C colorectal carcinoma. Lancet. 1994;343:1177–1183. doi: 10.1016/S0140-6736(94)92398-1. [DOI] [PubMed] [Google Scholar]
- 21.Lin R-H, Mamula MJ, Hardin JA, Janeway CA. Induction of autoreactive B cells allows priming of autoreactive T cells. J Exp Med. 1991;173:1433–1439. doi: 10.1084/jem.173.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Serreze DV, Chapman HD, Varnum DS, Hanson MS, Reifsnyder PC, Richard SD, Fleming SA, Leiter EH, Shultz LD. B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new “speed congenic” stock of NOD.Igμnull mice. J Exp Med. 1996;184:2049–2053. doi: 10.1084/jem.184.5.2049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Flexner S. The results of the serum treatment in thirteen hundred cases of epidemic meningitis. J Exp Med. 1913;17:553–553. doi: 10.1084/jem.17.5.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Heidelberger M, Avery OT. The soluble specific substance of pneumococcus. J Exp Med. 1923;38:73–79. doi: 10.1084/jem.38.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Kayhty H, Peltola H, Karanko V, et al. The protective level of serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b. J Infect Dis. 1983;147:1100–1100. doi: 10.1093/infdis/147.6.1100. [DOI] [PubMed] [Google Scholar]
- 26.Davidson NE, Gelmann EP, Lippman ME, Dickson RB. Epidermal growth factor gene expression in estrogen-positive and negative human breast cancer cell lines. Mol End. 1987;1:216–223. doi: 10.1210/mend-1-3-216. [DOI] [PubMed] [Google Scholar]
- 27.Lewis GD, Figari I, Fendly B, Wong WL, Carter P, Gorman C, Shepard HM. Differential responses of human tumor cell lines to anti pl85 HER2 monoclonal antibodies. Cancer Immol Immunother. 1993;37:255–263. doi: 10.1007/BF01518520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Hamilton WB, Helling F, Lloyd KO, Livingston PO. Ganglioside expression on human malignant melanoma assessed by quantitative immune thin layer chromatography. Int J Cancer. 1993;53:566–573. doi: 10.1002/ijc.2910530407. [DOI] [PubMed] [Google Scholar]
- 29.Hamilton WB, Helling F, Livingston PO. Ganglioside expression on sarcoma and small-cell lung carcinoma compared to tumors of neuroectodermal origin. Proc Am Assoc Cancer Res. 1993;34:491–491. [Google Scholar]
- 30.Helling F, Livingston PO. Ganglioside conjugate vaccines. Mol Chem Neuropathol. 1994;21:299–309. doi: 10.1007/BF02815357. [DOI] [PubMed] [Google Scholar]
- 31.Tai T, Cahan LD, Tsuchida T, Saxton RE, Irie RF, Morton DL. Immunogenicity of melanoma-associated ganliosides in cancer patients. Int J Cancer. 1985;35:607–607. doi: 10.1002/ijc.2910350507. [DOI] [PubMed] [Google Scholar]
- 32.Irie RF, Matsuki T, Morton DL. Human monoclonal antibody to ganglioside GM2 for melanoma treatment. Lancet. 1989;1:786–786. doi: 10.1016/S0140-6736(89)92606-8. [DOI] [PubMed] [Google Scholar]
- 33.Irie RF, Morton DL. Regression of cutaneous metastatic melanoma by intralesional injection with human monoclonal antibody to ganglioside GD2. Proc Natl Acad Sci USA. 1986;83:8694–8698. doi: 10.1073/pnas.83.22.8694. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Houghton AN, Mintzer D, Cordon-Cardo C, Welt S, Fliegel B, Vadhan S, Carswell E, Melamed MR, Oettgen HF, Old LJ. Mouse monoclonal antibody IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma. Proc Natl Acad Sci USA. 1985;82:1242–1246. doi: 10.1073/pnas.82.4.1242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Dippold WG, Bernhard H, Peter Dienes H, Meyer zum Buschenfelde K-H. Treatment of patients with malignant melanoma by monoclonal ganglioside antibodies. Eur J Cancer Clin Oncol. 1988;24:S65–S67. [Google Scholar]
- 36.Raymond J, Kirkwood J, Vlock D, Rabkin M, Day R, Whiteside T, Herberman R, Mascari R, Simon B. A phase 1B trial of murine monoclonal antibody R24 (anti-GD3) in metastatic melanoma (abstract) Proc Am Soc Clin Oncol. 1988;7:A958–A958. [Google Scholar]
- 37.Cheung N-K V, Lazarus H, Miraldi FD, Abramowsky CR, Kallie S, Saarinen UM, Spitzer T, Strandjord SE, Cocci PF, Berger NA. Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol. 1987;5:1430–1440. doi: 10.1200/JCO.1987.5.9.1430. [DOI] [PubMed] [Google Scholar]
- 38.Saleh MN, Khazaeli MB, Wheeler RH, Dropcho E, Liu T, Urist M, Miller DM, Lawson S, Dixon P, Russell CH, LoBuglio AF. Phase I trial of the murine monoclonal anti-GD2 antibody 14G9a in metastatic melanoma. Cancer Res. 1992;52:4342–4342. [PubMed] [Google Scholar]
- 39.Itzkowitz SH, Bloom EJ, Kokal WA, Modin G, Hakomori S-I, Kim YS. Sialosyl Tn: a novel mucin antigen associated with prognosis in colorectal cancer patients. Cancer. 1990;66:1960–1966. doi: 10.1002/1097-0142(19901101)66:9<1960::AID-CNCR2820660919>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
- 40.Collier BD, Abdel-Nabi H, Doerr RJ, Harwood SJ, Olsen J, Kaplan EH, Winzelberg GG, Grossman SJ, Krag DN, Michell EP. Immunoscintigraphy performed with In-111-labeled CYT-103 in the management of colorectal cancer: comparison with CT. Radiology. 1992;185:179–186. doi: 10.1148/radiology.185.1.1523304. [DOI] [PubMed] [Google Scholar]
- 41.Fung PYS, Madej M, Koganty RR, Longenecker BM. Active specific immunotherapy of a murine mammary adenocarcinoma using a synthetic tumor-associated glycoconjugate. Cancer Res. 1990;50:4308–4314. [PubMed] [Google Scholar]
- 42.Singhal A, Fohn M, Hakomori S-I. Induction of a-N-acetylgalactosamine-O-serine/threonine (Tn) antigen-mediated cellular immune response for active immunotherapy in mice. Cancer Res. 1991;51:1406–1411. [PubMed] [Google Scholar]
- 43.MacLean GD, Reddish MA, Koganty RR, Longenecker BM. Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic sTn vaccine. J Immunol. 1996;19:59–68. doi: 10.1097/00002371-199601000-00007. [DOI] [PubMed] [Google Scholar]
- 44.Lloyd KO. Blood group antigens as markers for normal differentiation and malignant change in human tissues. Am J Clin Pathol. 1987;87:129–139. doi: 10.1093/ajcp/87.1.129. [DOI] [PubMed] [Google Scholar]
- 45.Zhang S, Zhang HS, Cordon-Cardo C, Reuter VI, Lloyd KO, Livingston PO (1997) Selection of carbohydrate tumor antigens as targets for immune attack using immunohistochemistry. II. Blood group-related antigens. Int J Cancer (in press) [DOI] [PubMed]
- 46.Kudryashov V, Ragupathi G, Kim IJ, Livingston PO, Danishefsky SJ, Lloyd KO (1997) Immunogenicity of synthetic Lewis Y oligosaccharide-protein conjugates in mice: towards the design of anti-cancer vaccines. Cancer Immunol Immunother (in press) [DOI] [PMC free article] [PubMed]
- 47.Ragupathi G, Park TK, Zhang S, Kim IJ, Graeber K, Adluri S, Lloyd KO, Danishefsky SJ, Livingston PO. Immunization of mice with the synthetic hexasaccaride Globo H results in antibodies against human cancer cells. Angew Chem. 1997;36:125–128. doi: 10.1002/anie.199701251. [DOI] [Google Scholar]
- 48.Nilsson O, Brezicka FT, Holmgren J, Sorenson S, Svennerholm L, Yngvason F, Lindholm L. Detection of a ganglioside antigen associated with small cell lung carcinomas using monoclonal antibodies directed against fucosyl-GM1. Cancer Res. 1986;46:1403–1407. [PubMed] [Google Scholar]
- 49.Bilodeau MT, Park T-K, Hu S, Randolph JT, Danishefsky SJ, Livingston PO, Zhang S. Total synthesis of a human breast tumor associated antigen. J Amer Chem Soc. 1995;117:7840–7841. doi: 10.1021/ja00134a043. [DOI] [Google Scholar]
- 50.Komminoth P, Roth J, Lackie PM, Bitter-Suermann D, Heitz PU. Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids. Am J Pathol. 1991;139:297–304. [PMC free article] [PubMed] [Google Scholar]
- 51.Kaufmann SHE. Gamma/delta and other unconcentianal T lymphocytes: what do they see and what do they do? Proc Natl Acad Sci USA. 1996;93:2272–2279. doi: 10.1073/pnas.93.6.2272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Haurum JS, Arsequell G, Lellouch AC, Wong SYC, Dwek RA, McMichael AJ, Elliott T. Recognition of carbohydrate by major histocompatibility comples class I-restricted, glycopeptide-specific cytotoxic T lymphocytes. J Exp Med. 1994;180:739–744. doi: 10.1084/jem.180.2.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Michaelsson E, Malmstrom V, Reis S, Engstrom A, Burkhardt H, Holmdahl R. T cell recognition of carbohydrates on type II collagen. J Exp Med. 1994;180:745–749. doi: 10.1084/jem.180.2.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.Ishioka GY, Lamont AG, Thomson D, Bulbow N, Gaeta FCA, Sette A, Grey HM. MHC interaction and T cell recognition of carbohydrates and glycopeptides. J Immunol. 1992;148:2446–2451. [PubMed] [Google Scholar]
- 55.Eskola J, Kayrty H, Takuia AK, Peltola H, Ronneberg PR, Kha E, Pekkanen E, McVerry PH, Makela PH. A randomized prospective field trial of a conjugate vaccine in the protection of infants and young children against invasive Haemophilus influenzae type b disease. N Engl J Med. 1990;323:1381–1387. doi: 10.1056/NEJM199011153232004. [DOI] [PubMed] [Google Scholar]
- 56.Varki A. Biological roles of oligosaccharides: all of the theories are correct. Glycobiology. 1993;3:97–130. doi: 10.1093/glycob/3.2.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57.Kobata A. Structures and functions of the sugar chains of glycoproteins. Eur J Biochem. 1992;209:483–501. doi: 10.1111/j.1432-1033.1992.tb17313.x. [DOI] [PubMed] [Google Scholar]
- 58.Hart GW. Glycosylation. Curr Opin Cell Biol. 1992;4:1017–1023. doi: 10.1016/0955-0674(92)90134-X. [DOI] [PubMed] [Google Scholar]
- 59.Ashwell G, Harford J. Carbohydrate-specific receptors of the liver. Annu Rev Biochem. 1982;51:531–554. doi: 10.1146/annurev.bi.51.070182.002531. [DOI] [PubMed] [Google Scholar]
- 60.Rosen SD, Bertozzi CR. The selectins and their ligands. Curr Opin Cell Biol. 1994;6:663–673. doi: 10.1016/0955-0674(94)90092-2. [DOI] [PubMed] [Google Scholar]
- 61.Kelm S, Schauer R, Crocker PR. The sialoadhesins — a family of sialic acid-dependent cellular recognition molecules within the immunoglobulin superfamily. Glycoconjugate J. 1996;13:913–926. doi: 10.1007/BF01053186. [DOI] [PubMed] [Google Scholar]
- 62.Sawada R, Tsuboi S, Fukuda M. Differential E-selectin-dependent adhesion efficiency in sublines of a human colon cancer exhibiting distinct metastatic potentials. J Biol Chem. 1994;269:1425–1431. [PubMed] [Google Scholar]
- 63.Hakomori S-I. Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res. 1996;56:5309–5318. [PubMed] [Google Scholar]
- 64.Cheresh DA, Harper JR, Schulz G, Reisfeld RA. Localization of the gangliosides GD2 and GD3 in adhesion plaques and on the surface of human melanoma cells. Proc Natl Acad Sci USA. 1984;81:5767–5771. doi: 10.1073/pnas.81.18.5767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 65.Nakano J, Raj BKM, Asagami C, Lloyd KO. Human melanoma cell lines deficient in GD3 ganglioside expression exhibit altered growth and tumorigenic characteristics. J Invest Dermatol. 1996;107:543–548. doi: 10.1111/1523-1747.ep12582802. [DOI] [PubMed] [Google Scholar]
- 66.Tsuchida T, Saxton RE, Kmorton DL, et al. Gangliosides of human melanoma. J Natl Cancer Inst. 1987;78:45–54. doi: 10.1093/jnci/78.1.45. [DOI] [PubMed] [Google Scholar]
- 67.Zhang S, Cordon-Cardo C, Zhang HS, Reuter VE, Adluri S, Hamilton WB, Lloyd KO, Livingston PO (1997) Selection of carbohydrate tumor antigens as targets for immune attack using immunohistochemistry: I. Focus on gangliosides. Int J Cancer (in press) [DOI] [PubMed]
- 68.Springer GF. T and Tn, general carcinoma autoantigens. Science. 1984;224:1198–1206. doi: 10.1126/science.6729450. [DOI] [PubMed] [Google Scholar]
- 69.Adluri S, Helling F, Calves MJ, Lloyd KO, Livingston PO. Immunogenicity of synthetic TF- and sTn-KLH conjugates in colorectal carcinoma patients. Cancer Immunol Immunother. 1995;41:185–192. doi: 10.1007/BF01521345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 70.Mordoh J, Silva C, Albarellos M, Bravo AI, Kairiyama C. Phase I clinical trial in cancer patients of a new monoclonal antibody FC-2.15 reacting with tumor proliferating cells. J Immunother. 1995;17:151–180. doi: 10.1097/00002371-199504000-00004. [DOI] [PubMed] [Google Scholar]
- 71.Capurro M, Bover L, Portela P, Livingston PO, Mordoh J (1997) FC-2.15, a monoclonal antibody active against human breast cancer, specifically recognizes Lewis X hapten. Cancer Immunol Immunother (in press) [DOI] [PMC free article] [PubMed]
- 72.Lammie GA, Cheung NKV, Gerald W, Rosenblum M, Cordon-Cardo C. Ganglioside GD2 expression in the human nervous system and in neuroblastomas — an immunohistochemical study. Intl J Oncol. 1993;3:909–915. doi: 10.3892/ijo.3.5.909. [DOI] [PubMed] [Google Scholar]
- 73.Merritt WD, Taylor BJ, Der-Minassian V, Reaman GH. Coexpression of GD3 ganglioside with CD45RO in resting and activated human T lymphocytes. Cell Immunol. 1996;173:131–148. doi: 10.1006/cimm.1996.0259. [DOI] [PubMed] [Google Scholar]
- 74.Sopori ML, Donaldson LA, Savage SM. T Lympocyte heterogeneity in the rat. III. Autoreactive T cells are activated by B cells. Cell Immun. 1990;128:427–437. doi: 10.1016/0008-8749(90)90038-S. [DOI] [PubMed] [Google Scholar]