Skip to main content
SpringerLink
Log in

Targeting Glycans for Immunotherapy of Human Cancers

  • Chapter
  • First Online:
Glycosignals in Cancer: Mechanisms of Malignant Phenotypes

  • 803 Accesses

Abstract

Surface carbohydrate-containing molecules, such as glycoproteins and glycolipids, have been shown to play crucial regulatory roles in the normal physiological process as well as in pathological conditions including tumor progression. Those glycans which are overexpressed on the surface of tumor cells, but not detected or only weakly expressed in some limited normal tissues, are designated as tumor-associated carbohydrate antigens (TACAs). These TACAs may serve as potential targets for immunotherapy. The biological functions of TACAs and therapeutic strategies against TACAs will be addressed in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ajani JA et al (2000) A multi-institutional phase II study of BMS-182248-01 (BR96-doxorubicin conjugate) administered every 21 days in patients with advanced gastric adenocarcinoma. Cancer J 6(2):78–81

    CAS  PubMed  Google Scholar 

  • Albertini MR et al (2012) Phase II trial of hu14.18-IL2 for patients with metastatic melanoma. Cancer Immunol Immunother 61(12):2261–2271

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Alvarez-Rueda N et al (2011) A monoclonal antibody to O-acetyl-GD2 ganglioside and not to GD2 shows potent anti-tumor activity without peripheral nervous system cross-reactivity. PLoS ONE 6(9), e25220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Barker E et al (1991) Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Res 51(1):144–149

    CAS  PubMed  Google Scholar 

  • Battula VL et al (2012) Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis. J Clin Invest 122(6):2066–2078

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Becker R et al (2002) Phase I clinical trial on adjuvant active immunotherapy of human gliomas with GD2-conjugate. Br J Neurosurg 16(3):269–275

    Article  CAS  PubMed  Google Scholar 

  • Biswas K et al (2006) GM2 expression in renal cell carcinoma: potential role in tumor-induced T-cell dysfunction. Cancer Res 66(13):6816–6825

    Article  CAS  PubMed  Google Scholar 

  • Biswas S et al (2009) Elevated levels of select gangliosides in T cells from renal cell carcinoma patients is associated with T cell dysfunction. J Immunol 183(8):5050–5058

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bjerkvig R et al (1991) Anti-GM2 monoclonal antibodies induce necrosis in GM2-rich cultures of a human glioma cell line. Cancer Res 51(17):4643–4648

    CAS  PubMed  Google Scholar 

  • Borsig L et al (2001) Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci USA 98(6):3352–3357

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Borsig L et al (2002) Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci USA 99(4):2193–2198

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Carubia JM et al (1984) Gangliosides of normal and neoplastic human melanocytes. Biochem Biophys Res Commun 120(2):500–504

    Article  CAS  PubMed  Google Scholar 

  • Cazet A et al (2012) The ganglioside G(D2) induces the constitutive activation of c-Met in MDA-MB-231 breast cancer cells expressing the G(D3) synthase. Glycobiology 22(6):806–816

    Article  CAS  PubMed  Google Scholar 

  • Chang WW et al (2008) Expression of Globo H and SSEA3 in breast cancer stem cells and the involvement of fucosyltransferases 1 and 2 in Globo H synthesis. Proc Natl Acad Sci USA 105(33):11667–11672

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chapman PB et al (2000) Vaccination with a bivalent G(M2) and G(D2) ganglioside conjugate vaccine: a trial comparing doses of G(D2)-keyhole limpet hemocyanin. Clin Cancer Res 6(12):4658–4662

    CAS  PubMed  Google Scholar 

  • Chen YX et al (2013) Effect of tumor gangliosides on tyrosine phosphorylation of p125FAK in platelet adhesion to collagen. Oncol Rep 29(1):343–348

    PubMed  Google Scholar 

  • Cheng JY et al (2014) Globo-H ceramide shed from cancer cells triggers translin-associated factor X-dependent angiogenesis. Cancer Res 74:6856–6866

    Article  CAS  PubMed  Google Scholar 

  • Cheung NK et al (1985) Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells. Cancer Res 45(6):2642–2649

    CAS  PubMed  Google Scholar 

  • Cheung NK et al (1986) Complete tumor ablation with iodine 131-radiolabeled disialoganglioside GD2-specific monoclonal antibody against human neuroblastoma xenografted in nude mice. J Natl Cancer Inst 77(3):739–745

    CAS  PubMed  Google Scholar 

  • Cheung NK et al (1987) Ganglioside GD2 specific monoclonal antibody 3F8: a phase I study in patients with neuroblastoma and malignant melanoma. J Clin Oncol 5(9):1430–1440

    CAS  PubMed  Google Scholar 

  • Cheung NK et al (1998a) 3F8 monoclonal antibody treatment of patients with stage 4 neuroblastoma: a phase II study. Int J Oncol 12(6):1299–1306

    CAS  PubMed  Google Scholar 

  • Cheung NK et al (1998b) Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. J Clin Oncol 16(9):3053–3060

    CAS  PubMed  Google Scholar 

  • Cheung NK et al (2000) Induction of Ab3 and Ab3’ antibody was associated with long-term survival after anti-G(D2) antibody therapy of stage 4 neuroblastoma. Clin Cancer Res 6(7):2653–2660

    CAS  PubMed  Google Scholar 

  • Cheung NK et al (2006) FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor. J Clin Oncol 24(18):2885–2890

    Article  CAS  PubMed  Google Scholar 

  • Cheung NK et al (2012) Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte-macrophage colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with stage 4 neuroblastoma in first remission. J Clin Oncol 30(26):3264–3270

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chu JW, Sharom FJ (1993) Gangliosides inhibit T-lymphocyte proliferation by preventing the interaction of interleukin-2 with its cell surface receptors. Immunology 79(1):10–17

    PubMed Central  CAS  PubMed  Google Scholar 

  • Chung TW et al (2009) Ganglioside GM3 inhibits VEGF/VEGFR-2-mediated angiogenesis: direct interaction of GM3 with VEGFR-2. Glycobiology 19(3):229–239

    Article  CAS  PubMed  Google Scholar 

  • Crespo FA et al (2006) The immunoregulatory effects of gangliosides involve immune deviation favoring type-2 T cell responses. J Leukoc Biol 79(3):586–595

    Article  CAS  PubMed  Google Scholar 

  • Das T et al (2008) GM1 and tumor necrosis factor-alpha, overexpressed in renal cell carcinoma, synergize to induce T-cell apoptosis. Cancer Res 68(6):2014–2023

    Article  CAS  PubMed  Google Scholar 

  • Delgado DC et al (2010) Genotypes of NK cell KIR receptors, their ligands, and Fcgamma receptors in the response of neuroblastoma patients to Hu14.18-IL2 immunotherapy. Cancer Res 70(23):9554–9561

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dennis JW et al (1987) Beta 1–6 branching of Asn-linked oligosaccharides is directly associated with metastasis. Science 236(4801):582–585

    Article  CAS  PubMed  Google Scholar 

  • Eggermont AM et al (2013) Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection of primary tumor > 1.5 mm in patients with stage II melanoma: results of the EORTC 18961 randomized phase III trial. J Clin Oncol 31(30):3831–3837

    Article  CAS  PubMed  Google Scholar 

  • Eller CH et al (2015) Human cancer antigen globo H is a cell-surface ligand for human ribonuclease 1. ACS Cen Sci 1(4):181–190

    Article  CAS  Google Scholar 

  • Fernandes B et al (1991) Beta 1–6 branched oligosaccharides as a marker of tumor progression in human breast and colon neoplasia. Cancer Res 51(2):718–723

    CAS  PubMed  Google Scholar 

  • Figarella-Branger DF, Durbec PL, Rougon GN (1990) Differential spectrum of expression of neural cell adhesion molecule isoforms and L1 adhesion molecules on human neuroectodermal tumors. Cancer Res 50(19):6364–6370

    CAS  PubMed  Google Scholar 

  • Foon KA et al (1998) Antibody responses in melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2. Clin Cancer Res 4(5):1117–1124

    CAS  PubMed  Google Scholar 

  • Foon KA et al (2000) Clinical and immune responses in advanced melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2. J Clin Oncol 18(2):376–384

    CAS  PubMed  Google Scholar 

  • Frost JD et al (1997) A phase I/IB trial of murine monoclonal anti-GD2 antibody 14.G2a plus interleukin-2 in children with refractory neuroblastoma: a report of the Children’s Cancer Group. Cancer 80(2):317–333

    Article  CAS  PubMed  Google Scholar 

  • Fujii Y et al (2005) Murine glycosyltransferases responsible for the expression of globo-series glycolipids: cDNA structures, mRNA expression, and distribution of their products. Glycobiology 15(12):1257–1267

    Article  CAS  PubMed  Google Scholar 

  • Gao J et al (2014) Expression of CD147 and Lewis y antigen in ovarian cancer and their relationship to drug resistance. Med Oncol 31(5):920

    Article  PubMed  CAS  Google Scholar 

  • Gilewski T et al (2001) Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: a phase I trial. Proc Natl Acad Sci USA 98(6):3270–3275

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gillies SD, Lo KM, Wesolowski J (1989) High-level expression of chimeric antibodies using adapted cDNA variable region cassettes. J Immunol Methods 125(1–2):191–202

    Article  CAS  PubMed  Google Scholar 

  • Gilman AL et al (2009) Phase I study of ch14.18 with granulocyte-macrophage colony-stimulating factor and interleukin-2 in children with neuroblastoma after autologous bone marrow transplantation or stem-cell rescue: a report from the Children’s Oncology Group. J Clin Oncol 27(1):85–91

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gluer S et al (1998) Polysialylated neural cell adhesion molecule in childhood ganglioneuroma and neuroblastoma of different histological grade and clinical stage. Langenbecks Arch Surg 383(5):340–344

    Article  CAS  PubMed  Google Scholar 

  • Handgretinger R et al (1995) A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma. Eur J Cancer 31A(2):261–267

    Article  CAS  PubMed  Google Scholar 

  • Helling F et al (1995) GM2-KLH conjugate vaccine: increased immunogenicity in melanoma patients after administration with immunological adjuvant QS-21. Cancer Res 55(13):2783–2788

    CAS  PubMed  Google Scholar 

  • Hodi FS et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hoff SD et al (1989) Increased expression of sialyl-dimeric LeX antigen in liver metastases of human colorectal carcinoma. Cancer Res 49(24 Pt 1):6883–6888

    CAS  PubMed  Google Scholar 

  • Huang YL et al (2013) Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer. Proc Natl Acad Sci USA 110(7):2517–2522

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ibrahim NK et al (2013) Survival advantage in patients with metastatic breast cancer receiving endocrine therapy plus sialyl Tn-KLH vaccine: post Hoc analysis of a large randomized trial. J Cancer 4(7):577–584

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Irani DN, Lin KI, Griffin DE (1996) Brain-derived gangliosides regulate the cytokine production and proliferation of activated T cells. J Immunol 157(10):4333–4340

    CAS  PubMed  Google Scholar 

  • Itzkowitz SH et al (1986) Lewisx- and sialylated Lewisx-related antigen expression in human malignant and nonmalignant colonic tissues. Cancer Res 46(5):2627–2632

    CAS  PubMed  Google Scholar 

  • Itzkowitz SH et al (1989) Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. Cancer Res 49(1):197–204

    CAS  PubMed  Google Scholar 

  • Itzkowitz SH et al (1990) Sialosyl-Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients. Cancer 66(9):1960–1966

    Article  CAS  PubMed  Google Scholar 

  • Jacewicz M et al (1986) Pathogenesis of shigella diarrhea. XI. Isolation of a shigella toxin-binding glycolipid from rabbit jejunum and HeLa cells and its identification as globotriaosylceramide. J Exp Med 163(6):1391–1404

    Article  CAS  PubMed  Google Scholar 

  • Jin HJ et al (2010) GD2 expression is closely associated with neuronal differentiation of human umbilical cord blood-derived mesenchymal stem cells. Cell Mol Life Sci 67(11):1845–1858

    Article  CAS  PubMed  Google Scholar 

  • Julien S, Videira PA, Delannoy P (2012) Sialyl-tn in cancer: (how) did we miss the target? Biomolecules 2(4):435–466

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kannagi R (1997) Carbohydrate-mediated cell adhesion involved in hematogenous metastasis of cancer. Glycoconj J 14(5):577–584

    Article  CAS  PubMed  Google Scholar 

  • Kannagi R et al (1983) New globoseries glycosphingolipids in human teratocarcinoma reactive with the monoclonal antibody directed to a developmentally regulated antigen, stage-specific embryonic antigen 3. J Biol Chem 258(14):8934–8942

    CAS  PubMed  Google Scholar 

  • Kantoff PW et al (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363(5):411–422

    Article  CAS  PubMed  Google Scholar 

  • Kimata H, Yoshida A (1996) Inhibition of spontaneous immunoglobulin production by ganglioside GM2 in human B cells. Clin Immunol Immunopathol 79(2):197–202

    Article  CAS  PubMed  Google Scholar 

  • King DM et al (2004) Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. J Clin Oncol 22(22):4463–4473

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kirkwood JM et al (2001) High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J Clin Oncol 19(9):2370–2380

    CAS  PubMed  Google Scholar 

  • Kjeldsen T et al (1988) Preparation and characterization of monoclonal antibodies directed to the tumor-associated O-linked sialosyl-2----6 alpha-N-acetylgalactosaminyl (sialosyl-Tn) epitope. Cancer Res 48(8):2214–2220

    CAS  PubMed  Google Scholar 

  • Klein G et al (1983) Expression of the BLA antigen, defined by the monoclonal 38.13 antibody, on Burkitt lymphoma lines, lymphoblastoid cell lines, their hybrids and other B-cell lymphomas and leukemias. Int J Cancer 31(5):535–542

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi H, Terao T, Kawashima Y (1992) Serum sialyl Tn as an independent predictor of poor prognosis in patients with epithelial ovarian cancer. J Clin Oncol 10(1):95–101

    CAS  PubMed  Google Scholar 

  • Kojima Y et al (2000) Molecular cloning of globotriaosylceramide/CD77 synthase, a glycosyltransferase that initiates the synthesis of globo series glycosphingolipids. J Biol Chem 275(20):15152–15156

    Article  CAS  PubMed  Google Scholar 

  • Kondo Y et al (2013) TLR4-MD-2 complex is negatively regulated by an endogenous ligand, globotetraosylceramide. Proc Natl Acad Sci USA 110(12):4714–4719

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Krug LM et al (2004) Vaccination of small cell lung cancer patients with polysialic acid or N-propionylated polysialic acid conjugated to keyhole limpet hemocyanin. Clin Cancer Res 10(3):916–923

    Article  CAS  PubMed  Google Scholar 

  • Krug LM et al (2012) Immunization with N-propionyl polysialic acid-KLH conjugate in patients with small cell lung cancer is safe and induces IgM antibodies reactive with SCLC cells and bactericidal against group B meningococci. Cancer Immunol Immunother 61(1):9–18

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kushner BH et al (2014) Phase I trial of a bivalent gangliosides vaccine in combination with beta-glucan for high-risk neuroblastoma in second or later remission. Clin Cancer Res 20(5):1375–1382

    Article  CAS  PubMed  Google Scholar 

  • Ladisch S, Becker H, Ulsh L (1992) Immunosuppression by human gangliosides: I. Relationship of carbohydrate structure to the inhibition of T cell responses. Biochim Biophys Acta 1125(2):180–188

    Article  CAS  PubMed  Google Scholar 

  • Leivonen M et al (2001) STn and prognosis in breast cancer. Oncology 61(4):299–305

    Article  CAS  PubMed  Google Scholar 

  • Liang YJ et al (2013) Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells. Proc Natl Acad Sci USA 110(13):4968–4973

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu Y et al (2014a) Tumor gangliosides accelerate murine tumor angiogenesis. Angiogenesis 17(3):563–571

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Liu B et al (2014b) Endothelin A receptor antagonism enhances inhibitory effects of anti-ganglioside GD2 monoclonal antibody on invasiveness and viability of human osteosarcoma cells. PLoS ONE 9(4), e93576

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Livingston PO et al (1994a) Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside. J Clin Oncol 12(5):1036–1044

    CAS  PubMed  Google Scholar 

  • Livingston PO et al (1994b) Phase 1 trial of immunological adjuvant QS-21 with a GM2 ganglioside-keyhole limpet haemocyanin conjugate vaccine in patients with malignant melanoma. Vaccine 12(14):1275–1280

    Article  CAS  PubMed  Google Scholar 

  • Louis CU et al (2011) Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 118(23):6050–6056

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lu P, Sharom FJ (1996) Immunosuppression by YAC-1 lymphoma: role of shed gangliosides. Cell Immunol 173(1):22–32

    Article  CAS  PubMed  Google Scholar 

  • Ma XC et al (1993) Expression of sialyl-Tn antigen is correlated with survival time of patients with gastric carcinomas. Eur J Cancer 29A(13):1820–1823

    Article  CAS  PubMed  Google Scholar 

  • MacLean GD et al (1996) Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic STn vaccine. J Immunother Emphasis Tumor Immunol 19(1):59–68

    Article  CAS  PubMed  Google Scholar 

  • Makino T et al (2001) Carbohydrate antigens as a risk factor for hematogenous recurrence of esophageal squamous cell carcinoma patients. Oncol Rep 8(5):981–985

    CAS  PubMed  Google Scholar 

  • Manfredi MG et al (1999) Gangliosides influence angiogenesis in an experimental mouse brain tumor. Cancer Res 59(20):5392–5397

    CAS  PubMed  Google Scholar 

  • Martinez C et al (2007) Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: a novel surface marker for the identification of MSCs. Blood 109(10):4245–4248

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Metelitsa LS et al (2002) Antidisialoganglioside/granulocyte macrophage-colony-stimulating factor fusion protein facilitates neutrophil antibody-dependent cellular cytotoxicity and depends on FcgammaRII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell adhesion and azurophil granule exocytosis. Blood 99(11):4166–4173

    Article  CAS  PubMed  Google Scholar 

  • Miles DW et al (1994) Expression of sialyl-Tn predicts the effect of adjuvant chemotherapy in node-positive breast cancer. Br J Cancer 70(6):1272–1275

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Miles D et al (2011) Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer. Oncologist 16(8):1092–1100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Miraldi FD et al (1986) Diagnostic imaging of human neuroblastoma with radiolabeled antibody. Radiology 161(2):413–418

    Article  CAS  PubMed  Google Scholar 

  • Miyake M et al (1992) Correlation of expression of H/Le(y)/Le(b) antigens with survival in patients with carcinoma of the lung. N Engl J Med 327(1):14–18

    Article  CAS  PubMed  Google Scholar 

  • Morioka N et al (1991) Gangliosides inhibit the proliferation of human T cells stimulated with interleukin-4 or interleukin-2. J Dermatol 18(8):447–453

    Article  CAS  PubMed  Google Scholar 

  • Motoo Y et al (1991) Serum sialyl-Tn antigen levels in patients with digestive cancers. Oncology 48(4):321–326

    Article  CAS  PubMed  Google Scholar 

  • Mueller BM et al (1990) Enhancement of antibody-dependent cytotoxicity with a chimeric anti-GD2 antibody. J Immunol 144(4):1382–1386

    CAS  PubMed  Google Scholar 

  • Mujoo K et al (1987) Disialoganglioside GD2 on human neuroblastoma cells: target antigen for monoclonal antibody-mediated cytolysis and suppression of tumor growth. Cancer Res 47(4):1098–1104

    CAS  PubMed  Google Scholar 

  • Mujoo K et al (1989) Functional properties and effect on growth suppression of human neuroblastoma tumors by isotype switch variants of monoclonal antiganglioside GD2 antibody 14.18. Cancer Res 49(11):2857–2861

    CAS  PubMed  Google Scholar 

  • Murata K et al (2004) Attachment of human colon cancer cells to vascular endothelium is enhanced by N-acetylglucosaminyltransferase V. Oncology 66(6):492–501

    Article  CAS  PubMed  Google Scholar 

  • Murray LJ et al (1985) Expression of Burkitt lymphoma-associated antigen (defined by the monoclonal antibody 38.13) on both normal and malignant germinal-centre B cells. Int J Cancer 36(5):561–565

    Article  CAS  PubMed  Google Scholar 

  • Murray JL et al (1994) Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors. J Clin Oncol 12(1):184–193

    CAS  PubMed  Google Scholar 

  • Nakamura K et al (1999) Apoptosis induction of human lung cancer cell line in multicellular heterospheroids with humanized antiganglioside GM2 monoclonal antibody. Cancer Res 59(20):5323–5330

    CAS  PubMed  Google Scholar 

  • Navid F et al (2014) Phase I trial of a novel anti-GD2 monoclonal antibody, Hu14.18K322A, designed to decrease toxicity in children with refractory or recurrent neuroblastoma. J Clin Oncol 32(14):1445–1452

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Neal ZC et al (2004a) Enhanced activity of hu14.18-IL2 immunocytokine against murine NXS2 neuroblastoma when combined with interleukin 2 therapy. Clin Cancer Res 10(14):4839–4847

    Article  CAS  PubMed  Google Scholar 

  • Neal ZC et al (2004b) NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy. Cancer Immunol Immunother 53(1):41–52

    Article  CAS  PubMed  Google Scholar 

  • Ohno S et al (2005a) Multiple roles of cyclooxygenase-2 in endometrial cancer. Anticancer Res 25(6A):3679–3687

    CAS  PubMed  Google Scholar 

  • Ohno Y et al (2005b) Role of cyclooxygenase-2 in immunomodulation and prognosis of endometrial carcinoma. Int J Cancer 114(5):696–701

    Article  CAS  PubMed  Google Scholar 

  • Ohno S et al (2006) Expression of Tn and sialyl-Tn antigens in endometrial cancer: its relationship with tumor-produced cyclooxygenase-2, tumor-infiltrated lymphocytes and patient prognosis. Anticancer Res 26(6A):4047–4053

    CAS  PubMed  Google Scholar 

  • Ohtsubo K, Marth JD (2006) Glycosylation in cellular mechanisms of health and disease. Cell 126(5):855–867

    Article  CAS  PubMed  Google Scholar 

  • Okuda T et al (2006) Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins. J Biol Chem 281(15):10230–10235

    Article  CAS  PubMed  Google Scholar 

  • Osenga KL et al (2006) A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children’s Oncology Group. Clin Cancer Res 12(6):1750–1759

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ozkaynak MF et al (2000) Phase I study of chimeric human/murine anti-ganglioside G(D2) monoclonal antibody (ch14.18) with granulocyte-macrophage colony-stimulating factor in children with neuroblastoma immediately after hematopoietic stem-cell transplantation: a children’s cancer group study. J Clin Oncol 18(24):4077–4085

    CAS  PubMed  Google Scholar 

  • Palaga T et al (2003) TCR-mediated Notch signaling regulates proliferation and IFN-gamma production in peripheral T cells. J Immunol 171(6):3019–3024

    Article  CAS  PubMed  Google Scholar 

  • Peguet-Navarro J et al (2003) Gangliosides from human melanoma tumors impair dendritic cell differentiation from monocytes and induce their apoptosis. J Immunol 170(7):3488–3494

    Article  CAS  PubMed  Google Scholar 

  • Pinho S et al (2007) Biological significance of cancer-associated sialyl-Tn antigen: modulation of malignant phenotype in gastric carcinoma cells. Cancer Lett 249(2):157–170

    Article  CAS  PubMed  Google Scholar 

  • Reis CA et al (2010) Alterations in glycosylation as biomarkers for cancer detection. J Clin Pathol 63(4):322–329

    Article  CAS  PubMed  Google Scholar 

  • Retter MW et al (2005) Characterization of a proapoptotic antiganglioside GM2 monoclonal antibody and evaluation of its therapeutic effect on melanoma and small cell lung carcinoma xenografts. Cancer Res 65(14):6425–6434

    Article  CAS  PubMed  Google Scholar 

  • Robert C et al (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372(4):320–330

    Article  CAS  PubMed  Google Scholar 

  • Robert C et al (2014) Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 384(9948):1109–1117

    Article  CAS  PubMed  Google Scholar 

  • Rosen SD, Bertozzi CR (1994) The selectins and their ligands. Curr Opin Cell Biol 6(5):663–673

    Article  CAS  PubMed  Google Scholar 

  • Roth J et al (1988a) Presence of the long chain form of polysialic acid of the neural cell adhesion molecule in Wilms’ tumor. Identification of a cell adhesion molecule as an oncodevelopmental antigen and implications for tumor histogenesis. Am J Pathol 133(2):227–240

    PubMed Central  CAS  PubMed  Google Scholar 

  • Roth J et al (1988b) Reexpression of poly(sialic acid) units of the neural cell adhesion molecule in Wilms tumor. Proc Natl Acad Sci USA 85(9):2999–3003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sabbatini PJ et al (2000) Immunization of ovarian cancer patients with a synthetic Lewis(y)-protein conjugate vaccine: a phase 1 trial. Int J Cancer 87(1):79–85

    Article  CAS  PubMed  Google Scholar 

  • Sabbatini PJ et al (2007) Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer. Clin Cancer Res 13(14):4170–4177

    Article  CAS  PubMed  Google Scholar 

  • Saleh MN et al (1992a) Phase I trial of the murine monoclonal anti-GD2 antibody 14G2a in metastatic melanoma. Cancer Res 52(16):4342–4347

    CAS  PubMed  Google Scholar 

  • Saleh MN et al (1992b) Phase I trial of the chimeric anti-GD2 monoclonal antibody ch14.18 in patients with malignant melanoma. Hum Antibodies Hybridomas 3(1):19–24

    CAS  PubMed  Google Scholar 

  • Saleh MN et al (1993) Generation of a human anti-idiotypic antibody that mimics the GD2 antigen. J Immunol 151(6):3390–3398

    CAS  PubMed  Google Scholar 

  • Savoldo B, Dotti G (2013) Chimeric antigen receptors (CARs) from bench-to-bedside. Immunol Lett 155(1–2):40–42

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schulz G et al (1984) Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma patients. Cancer Res 44(12 Pt 1):5914–5920

    CAS  PubMed  Google Scholar 

  • Seelentag WK et al (1998) Prognostic value of beta1,6-branched oligosaccharides in human colorectal carcinoma. Cancer Res 58(23):5559–5564

    CAS  PubMed  Google Scholar 

  • Sen G et al (1998) Induction of IgG antibodies by an anti-idiotype antibody mimicking disialoganglioside GD2. J Immunother 21(1):75–83

    Article  CAS  PubMed  Google Scholar 

  • Shibuya H et al (2012) Enhancement of malignant properties of human osteosarcoma cells with disialyl gangliosides GD2/GD3. Cancer Sci 103(9):1656–1664

    Article  CAS  PubMed  Google Scholar 

  • Shusterman S et al (2010) Antitumor activity of hu14.18-IL2 in patients with relapsed/refractory neuroblastoma: a Children’s Oncology Group (COG) phase II study. J Clin Oncol 28(33):4969–4975

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Slovin SF et al (1999) Carbohydrate vaccines in cancer: immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man. Proc Natl Acad Sci USA 96(10):5710–5715

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Slovin SF et al (2005) A bivalent conjugate vaccine in the treatment of biochemically relapsed prostate cancer: a study of glycosylated MUC-2-KLH and Globo H-KLH conjugate vaccines given with the new semi-synthetic saponin immunological adjuvant GPI-0100 OR QS-21. Vaccine 23(24):3114–3122

    Article  CAS  PubMed  Google Scholar 

  • Slovin SF et al (2007) A polyvalent vaccine for high-risk prostate patients: “are more antigens better?”. Cancer Immunol Immunother 56(12):1921–1930

    Article  CAS  PubMed  Google Scholar 

  • Sorkin LS et al (2010) Anti-GD(2) with an FC point mutation reduces complement fixation and decreases antibody-induced allodynia. Pain 149(1):135–142

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Springer GF (1984) T and Tn, general carcinoma autoantigens. Science 224(4654):1198–1206

    Article  CAS  PubMed  Google Scholar 

  • Suzuki Y et al (1987) Aberrant expression of ganglioside and asialoglycosphingolipid antigens in adult T-cell leukemia cells. Jpn J Cancer Res 78(10):1112–1120

    CAS  PubMed  Google Scholar 

  • Svennerholm L et al (1994) Gangliosides and allied glycosphingolipids in human peripheral nerve and spinal cord. Biochim Biophys Acta 1214(2):115–123

    Article  CAS  PubMed  Google Scholar 

  • Takamiya R et al (2013) The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-beta secretion from monocytes/macrophages through the DAP12-Syk pathway. Glycobiology 23(2):178–187

    Article  CAS  PubMed  Google Scholar 

  • Tanaka F et al (2001) Prognostic significance of polysialic acid expression in resected non-small cell lung cancer. Cancer Res 61(4):1666–1670

    CAS  PubMed  Google Scholar 

  • Terme M et al (2014) Chimeric antibody c.8B6 to O-acetyl-GD2 mediates the same efficient anti-neuroblastoma effects as therapeutic ch14.18 antibody to GD2 without antibody induced allodynia. PLoS ONE 9(2):e87210

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Thornton MV et al (2004) Degradation of NF-kappa B in T cells by gangliosides expressed on renal cell carcinomas. J Immunol 172(6):3480–3490

    Article  CAS  PubMed  Google Scholar 

  • Todeschini AR et al (2008) Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway. Proc Natl Acad Sci USA 105(6):1925–1930

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tozawa K et al (2005) Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma. Kidney Int 67(4):1391–1396

    Article  CAS  PubMed  Google Scholar 

  • Tsai YC et al (2013) A prevalent cancer associated glycan, globo H ceramide, induces immunosuppression by reducing Notch1 signaling. J Cancer Sci Ther 5(7):264–270

    Article  Google Scholar 

  • Tsuchida T et al (1987) Gangliosides of human melanoma. J Natl Cancer Inst 78(1):45–54

    CAS  PubMed  Google Scholar 

  • Uttenreuther-Fischer MM et al (1995a) Pharmacokinetics of anti-ganglioside GD2 mAb 14G2a in a phase I trial in pediatric cancer patients. Cancer Immunol Immunother 41(1):29–36

    Article  CAS  PubMed  Google Scholar 

  • Uttenreuther-Fischer MM, Huang CS, Yu AL (1995b) Pharmacokinetics of human-mouse chimeric anti-GD2 mAb ch14.18 in a phase I trial in neuroblastoma patients. Cancer Immunol Immunother 41(6):331–338

    Article  CAS  PubMed  Google Scholar 

  • Uzzo RG et al (1999) Renal cell carcinoma-derived gangliosides suppress nuclear factor-kappaB activation in T cells. J Clin Invest 104(6):769–776

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • van de Kar NC et al (1992) Tumor necrosis factor and interleukin-1 induce expression of the verocytotoxin receptor globotriaosylceramide on human endothelial cells: implications for the pathogenesis of the hemolytic uremic syndrome. Blood 80(11):2755–2764

    PubMed  Google Scholar 

  • van Setten PA et al (1996) Effects of verocytotoxin-1 on nonadherent human monocytes: binding characteristics, protein synthesis, and induction of cytokine release. Blood 88(1):174–183

    PubMed  Google Scholar 

  • Wiels J, Fellous M, Tursz T (1981) Monoclonal antibody against a lymphoma-associated antigen. Proc Natl Acad Sci USA 78(10):6485–6488

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wolfl M et al (2002) Gangliosides inhibit the development from monocytes to dendritic cells. Clin Exp Immunol 130(3):441–448

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Xu J et al (2013) Neural ganglioside GD2(+) cells define a subpopulation of mesenchymal stem cells in adult murine bone marrow. Cell Physiol Biochem 32(4):889–898

    Article  CAS  PubMed  Google Scholar 

  • Yanagisawa M, Yoshimura S, Yu RK (2011) Expression of GD2 and GD3 gangliosides in human embryonic neural stem cells. ASN Neuro 3(2):e00054

    Google Scholar 

  • Yankelevich M et al (2012) Anti-CD3 x anti-GD2 bispecific antibody redirects T-cell cytolytic activity to neuroblastoma targets. Pediatr Blood Cancer 59(7):1198–1205

    Article  PubMed Central  PubMed  Google Scholar 

  • Yoshida S et al (2001) Ganglioside G(D2) in small cell lung cancer cell lines: enhancement of cell proliferation and mediation of apoptosis. Cancer Res 61(10):4244–4252

    CAS  PubMed  Google Scholar 

  • Yu AL, Uttenreuther-Fischer MM, Kamps A (1995) Combined use of a human mouse chimeric anti-GD2 (ch14.18) and GM-CSF in the treatment of refractory neuroblastoma. Antibody Immunocon Radiopharm 8:12

    Google Scholar 

  • Yu AL et al (1997) Usefulness of a chimeric anti-GD2 (ch14.18) and GM-CSF for refractory neuroblastoma: A POG phase II study. Proc ASCO 16:1846

    Google Scholar 

  • Yu AL et al (1998) Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma. J Clin Oncol 16(6):2169–2180

    CAS  PubMed  Google Scholar 

  • Yu AL, Eskenazi A, Strother D (2001) A pilot study of anti-idiotype monoclonal antibody as tumor vaccine in patients with high risk neuroblastoma. Proc Am Soc Clin Oncol 20:1470

    Google Scholar 

  • Yu AL et al (2010) Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 363(14):1324–1334

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yuan M et al (1986) Comparison of T-antigen expression in normal, premalignant, and malignant human colonic tissue using lectin and antibody immunohistochemistry. Cancer Res 46(9):4841–4847

    CAS  PubMed  Google Scholar 

  • Zeng Y et al (2005) Anti-neuroblastoma effect of ch14.18 antibody produced in CHO cells is mediated by NK-cells in mice. Mol Immunol 42(11):1311–1319

    Article  CAS  PubMed  Google Scholar 

  • Zhang S et al (1997) Selection of tumor antigens as targets for immune attack using immunohistochemistry: II. Blood group-related antigens. Int J Cancer 73(1):50–56

    Article  CAS  PubMed  Google Scholar 

  • Zhang S et al (1998) Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers. Clin Cancer Res 4(2):295–302

    CAS  PubMed  Google Scholar 

  • Zhuang H et al (2013) Co-expression of Lewis y antigen with human epididymis protein 4 in ovarian epithelial carcinoma. PLoS ONE 8(7), e68994

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhuang H et al (2014) Overexpression of Lewis y antigen promotes human epididymis protein 4-mediated invasion and metastasis of ovarian cancer cells. Biochimie 105:91–98

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, No.5, Fu-Shin St. Kuei Shang, 333, Taoyuan, Taiwan

    Jung-Tung Hung & Alice L. Yu

  2. University of California in San Diego Medical Center, 200 W Arbor Drive, San Diego, 92103, CA, USA

    Alice L. Yu

Authors
  1. Jung-Tung Hung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alice L. Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alice L. Yu .

Editor information

Editors and Affiliations

  1. Biomedical Sciences, Chubu University, Kasugai, Japan

    Koichi Furukawa

  2. Glycobiology Unit, Sanford-Burnham Med Res Inst, La Jolla, California, USA

    Minoru Fukuda

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Japan

About this chapter

Cite this chapter

Hung, JT., Yu, A.L. (2016). Targeting Glycans for Immunotherapy of Human Cancers. In: Furukawa, K., Fukuda, M. (eds) Glycosignals in Cancer: Mechanisms of Malignant Phenotypes . Springer, Tokyo. https://doi.org/10.1007/978-4-431-55939-9_11

Download citation

Publish with us

Policies and ethics

Search

Navigation