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Review

Carbohydrate-based vaccines: challenges and opportunities

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Pages 1257-1274 | Published online: 09 Jan 2014

References

  • Varki A. Biological roles of oligosaccharides: all of the theories are correct. Glycobiology3(2), 97–130 (1993).
  • Paulson JC, Blixt O, Collins BE. Sweet spots in functional glycomics. Nat. Chem. Biol.2(5), 238–248 (2006).
  • Francis T, Tillett WS. Cutaneous reactions in pneumonia. The development of antibodies following the intradermal injection of type-specific polysaccharide. J. Exp. Med.52(4), 573–585 (1930).
  • Macleod CM, Hodges RG, Heidelberger M, Bernhard WG. Prevention of pneumococcal pneumonia by immunization with specific capsular polysaccharides. J. Exp. Med.82(6), 445–465 (1945).
  • Heidelberger M, Dilapi MM, Siegel M, Walter AW. Persistence of antibodies in human subjects injected with pneumococcal polysaccharides. J. Immunol.65(5), 535–541 (1950).
  • Robbins JB, Austrian R, Lee CJ et al. Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cross-reactive types within groups. J. Infect. Dis.148(6), 1136–1159 (1983).
  • Avery OT, Goebel WF. Chemo-immunological studies on conjugated carbohydrate-proteins: II. Immunological specificity of synthetic sugar–protein antigens. J. Exp. Med.50(4), 533–550 (1929).
  • Jones C. Vaccines based on the cell surface carbohydrates of pathogenic bacteria. An. Acad. Bras. Cienc.77(2), 293–324 (2005).
  • Meningococcal vaccines. MMWR Morb. Mortal. Wkly Rep.34(18), 255–259 (1985).
  • Reingold AL, Broome CV, Hightower AW et al. Age-specific differences in duration of clinical protection after vaccination with meningococcal polysaccharide A vaccine. Lancet2(8447), 114–118 (1985).
  • Wilder-Smith A. Meningococcal disease: risk for international travellers and vaccine strategies. Travel Med. Infect. Dis.6(4), 182–186 (2008).
  • Bilukha OO, Rosenstein N. Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep.54(RR-7), 1–21 (2005).
  • Licensure of a meningococcal conjugate vaccine (Menveo) and guidance for use – Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb. Mortal. Wkly Rep.59(9), 273 (2010).
  • Jennings HJ, Roy R, Gamian A. Induction of meningococcal group B polysaccharide-specific IgG antibodies in mice by using an N-propionylated B polysaccharide–tetanus toxoid conjugate vaccine. J. Immunol.137(5), 1708–1713 (1986).
  • Fusco PC, Michon F, Tai JY, Blake MS. Preclinical evaluation of a novel group B meningococcal conjugate vaccine that elicits bactericidal activity in both mice and nonhuman primates. J. Infect. Dis.175(2), 364–372 (1997).
  • Bruge J, Bouveret-Le Cam N, Danve B, Rougon G, Schulz D. Clinical evaluation of a group B meningococcal N-propionylated polysaccharide conjugate vaccine in adult, male volunteers. Vaccine22(9–10), 1087–1096 (2004).
  • Sniadack DH, Schwartz B, Lipman H et al. Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children – implications for vaccine strategies. Pediatr. Infect. Dis. J.14(6), 503–510 (1995).
  • Kirkwood BR, Gove S, Rogers S, Lob-Levyt J, Arthur P, Campbell H. Potential interventions for the prevention of childhood pneumonia in developing countries: a systematic review. Bull. World Health Organ.73(6), 793–798 (1995).
  • Shapiro ED, Berg AT, Austrian R et al. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N. Engl. J. Med.325(21), 1453–1460 (1991).
  • Melegaro A, Edmunds WJ. The 23-valent pneumococcal polysaccharide vaccine. Part I. Efficacy of PPV in the elderly: a comparison of meta-analyses. Eur. J. Epidemiol.19(4), 353–363 (2004).
  • Oosterhuis-Kafeja F, Beutels P, Van Damme P. Immunogenicity, efficacy, safety and effectiveness of pneumococcal conjugate vaccines (1998–2006). Vaccine25(12), 2194–2212 (2007).
  • Wuorimaa T, Kayhty H. Current state of pneumococcal vaccines. Scand J. Immunol.56(2), 111–129 (2002).
  • Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children – Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb. Mortal. Wkly Rep.59(9), 258–261 (2010).
  • Atkinson W, Hamborsky J, McIntyre L, Wolfe S (Eds). Epidemiology and Prevention of Vaccine-Preventable Diseases (9th edition). Centers for Disease Control and Prevention, GA, USA (2006).
  • Kayhty H, Karanko V, Peltola H, Makela PH. Serum antibodies after vaccination with Haemophilus influenzae type b capsular polysaccharide and responses to reimmunization: no evidence of immunologic tolerance or memory. Pediatrics74(5), 857–865 (1984).
  • Guo ZW, Boons GJ. Chapter 2: preparation of glycoconjugate vaccines. In: Carbohydrate based Vaccines and Immunotherapies. Jogn A (Ed.). Wiley & Sons, Inc., NJ, USA, 55–88 (2009).
  • Anderson PW, Pichichero ME, Insel RA, Betts R, Eby R, Smith DH. Vaccines consisting of periodate-cleaved oligosaccharides from the capsule of Haemophilus influenzae type b coupled to a protein carrier: structural and temporal requirements for priming in the human infant. J. Immunol.137(4), 1181–1186 (1986).
  • Schneerson R, Barrera O, Sutton A, Robbins JB. Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates. J. Exp. Med.152(2), 361–376 (1980).
  • Marburg S, Jorn D, Tolman RL et al. Bimolecular chemistry of macromolecules – synthesis of bacterial polysaccharide conjugates with Neisseria meningitidis membrane-protein. J. Am. Chem. Soc.108(17), 5282–5287 (1986).
  • Verez-Bencomo V, Fernandez-Santana V, Hardy E et al. A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b. Science305(5683), 522–525 (2004).
  • Torano G, Toledo ME, Baly A et al. Phase I clinical evaluation of a synthetic oligosaccharide-protein conjugate vaccine against Haemophilus influenzae type b in human adult volunteers. Clin. Vaccine Immunol.13(9), 1052–1056 (2006).
  • Schofield L, Hewitt MC, Evans K, Siomos MA, Seeberger PH. Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature418(6899), 785–789 (2002).
  • Gerold P, Schofield L, Blackman MJ, Holder AA, Schwarz RT. Structural analysis of the glycosyl-phosphatidylinositol membrane anchor of the merozoite surface proteins-1 and -2 of Plasmodium falciparum. Mol. Biochem. Parasitol.75(2), 131–143 (1996).
  • Schmidt A, Schwarz RT, Gerold P. Plasmodium falciparum: asexual erythrocytic stages synthesize two structurally distinct free and protein-bound glycosylphosphatidylinositols in a maturation-dependent manner. Exp. Parasitol.88(2), 95–102 (1998).
  • Hewitt MC, Snyder DA, Seeberger PH. Rapid synthesis of a glycosylphosphatidylinositol-based malaria vaccine using automated solid-phase oligosaccharide synthesis. J. Am. Chem. Soc.124(45), 13434–13436 (2002).
  • Kamena F, Tamborrini M, Liu X et al. Synthetic GPI array to study antitoxic malaria response. Nat. Chem. Biol.4(4), 238–240 (2008).
  • Desjeux P. Leishmaniasis: current situation and new perspectives. Comp. Immunol. Microbiol. Infect. Dis.27(5), 305–318 (2004).
  • Mahoney AB, Sacks DL, Saraiva E, Modi G, Turco SJ. Intra-species and stage-specific polymorphisms in lipophosphoglycan structure control Leishmania donovani–sand fly interactions. Biochemistry38(31), 9813–9823 (1999).
  • Liu X, Siegrist S, Amacker M, Zurbriggen R, Pluschke G, Seeberger PH. Enhancement of the immunogenicity of synthetic carbohydrates by conjugation to virosomes: a leishmaniasis vaccine candidate. ACS Chem. Biol.1(3), 161–164 (2006).
  • Rogers ME, Sizova OV, Ferguson MA, Nikolaev AV, Bates PA. Synthetic glycovaccine protects against the bite of leishmania-infected sand flies. J. Infect. Dis.194(4), 512–518 (2006).
  • Routier FH, Nikolaev AV, Ferguson MA. The preparation of neoglycoconjugates containing inter-saccharide phosphodiester linkages as potential anti-Leishmania vaccines. Glycoconj. J.16(12), 773–780 (1999).
  • Mendonca-Previato L, Todeschini AR, Heise N, Previato JO. Protozoan parasite-specific carbohydrate structures. Curr. Opin. Struct. Biol.15(5), 499–505 (2005).
  • Ragupathi G. Carbohydrate antigens as targets for active specific immunotherapy. Cancer Immunol. Immunother.43(3), 152–157 (1996).
  • Hakomori S. Tumor-associated carbohydrate antigens defining tumor malignancy: basis for development of anti-cancer vaccines. Adv. Exp. Med. Biol.491, 369–402 (2001).
  • Livingston PO, Wong GY, Adluri S et al. 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 (1994).
  • 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.66(2), 249–254 (1981).
  • Schindlbeck C, Jeschke U, Schulze Set al. Prognostic impact of Thomsen–Friedenreich tumor antigen and disseminated tumor cells in the bone marrow of breast cancer patients. Breast Cancer Res. Treat.101(1), 17–25 (2007).
  • Buskas T, Thompson P, Boons GJ. Immunotherapy for cancer: synthetic carbohydrate-based vaccines. Chem. Commun.36, 5335–5349 (2009).
  • Guo Z, Wang Q. Recent development in carbohydrate-based cancer vaccines. Curr. Opin. Chem. Biol.13(5–6), 608–617 (2009).
  • Zhu J, Warren JD, Danishefsky SJ. Synthetic carbohydrate-based anticancer vaccines: the Memorial Sloan-Kettering experience. Expert Rev. Vaccines8(10), 1399–1413 (2009).
  • Astronomo RD, Burton DR. Carbohydrate vaccines: developing sweet solutions to sticky situations? Nat. Rev. Drug Discov.9(4), 308–324 (2010).
  • Helling F, Shang A, Calves M et al. GD3 vaccines for melanoma: superior immunogenicity of keyhole limpet hemocyanin conjugate vaccines. Cancer Res.54(1), 197–203 (1994).
  • Zhang H, Zhang S, Cheung NK, Ragupathi G, Livingston PO. Antibodies against GD2 ganglioside can eradicate syngeneic cancer micrometastases. Cancer Res.58(13), 2844–2849 (1998).
  • Helling F, Zhang S, Shang A et al. GM2–KLH conjugate vaccine: increased immunogenicity in melanoma patients after administration with immunological adjuvant QS-21. Cancer Res.55(13), 2783–2788 (1995).
  • Slovin SF, Keding SJ, Ragupathi G. Carbohydrate vaccines as immunotherapy for cancer. Immunol. Cell Biol.83(4), 418–428 (2005).
  • Ragupathi G, Park TK, Zhang SL et al. Immunization of mice with a fully synthetic globo H antigen results in antibodies against human cancer cells: a combined chemical–immunological approach to the fashioning of an anticancer vaccine. Angew Chem. Int. Ed. Engl.36(1–2), 125–128 (1997).
  • Slovin SF, Ragupathi G, Adluri S et al. Carbohydrate vaccines in cancer: immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man. Proc. Natl Acad. Sci. USA96(10), 5710–5715 (1999).
  • Gilewski T, Ragupathi G, Bhuta S et al. Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: a Phase I trial. Proc. Natl Acad. Sci. USA98(6), 3270–3275 (2001).
  • Dickler MN, Ragupathi G, Liu NX et al. Immunogenicity of a fucosyl–GM1–keyhole limpet hemocyanin conjugate vaccine in patients with small cell lung cancer. Clin. Cancer Res.5(10), 2773–2779 (1999).
  • Sabbatini PJ, Kudryashov V, Ragupathi G et al. Immunization of ovarian cancer patients with a synthetic Lewis(y)-protein conjugate vaccine: a Phase 1 trial. Int. J. Cancer87(1), 79–85 (2000).
  • Kuduk SD, Schwarz JB, Chen XT et al. Synthetic and immunological studies on clustered modes of mucin-related Tn and TF O-linked antigens: the preparation of a glycopeptide-based vaccine for clinical trials against prostate cancer. J. Am. Chem. Soc.120(48), 12474–12485 (1998).
  • Slovin SF, Ragupathi G, Musselli C et al. Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate cancer: clinical trial results with α-N-acetylgalactosamine-O-serine/threonine conjugate vaccine. J. Clin. Oncol.21(23), 4292–4298 (2003).
  • Gilewski TA, Ragupathi G, Dickler M et al. Immunization of high-risk breast cancer patients with clustered STn–KLH conjugate plus the immunologic adjuvant QS-21. Clin. Cancer Res.13(10), 2977–2985 (2007).
  • Zhu J, Wan Q, Ragupathi G, George CM, Livingston PO, Danishefsky SJ. Biologics through chemistry: total synthesis of a proposed dual-acting vaccine targeting ovarian cancer by orchestration of oligosaccharide and polypeptide domains. J. Am. Chem. Soc.131(11), 4151–4158 (2009).
  • Slovin SF, Ragupathi G, Fernandez C et al. A polyvalent vaccine for high-risk prostate patients: “are more antigens better?”. Cancer Immunol. Immunother.56(12), 1921–1930 (2007).
  • Sabbatini PJ, Ragupathi G, Hood C et al. 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 (2007).
  • Keding SJ, Danishefsky SJ. Prospects for total synthesis: a vision for a totally synthetic vaccine targeting epithelial tumors. Proc. Natl Acad. Sci. USA101(33), 11937–11942 (2004).
  • Ragupathi G, Koide F, Livingston PO et al. Preparation and evaluation of unimolecular pentavalent and hexavalent antigenic constructs targeting prostate and breast cancer: a synthetic route to anticancer vaccine candidates. J. Am. Chem. Soc.128(8), 2715–2725 (2006).
  • Zhu J, Wan Q, Lee D et al. From synthesis to biologics: preclinical data on a chemistry derived anticancer vaccine. J. Am. Chem. Soc.131(26), 9298–9303 (2009).
  • Lee D, Danishefsky SJ. ‘Biologic’ level structures through chemistry: a total synthesis of a unimolecular pentavalent MUCI glycopeptide construct. Tetrahedron Lett.50(19), 2167–2170 (2009).
  • Buskas T, Li Y, Boons GJ. The immunogenicity of the tumor-associated antigen Lewis(y) may be suppressed by a bifunctional cross-linker required for coupling to a carrier protein. Chem. Eur. J.10(14), 3517–3524 (2004).
  • Schutze MP, Leclerc C, Jolivet M, Audibert F, Chedid L. Carrier-induced epitopic suppression, a major issue for future synthetic vaccines. J. Immunol.135(4), 2319–2322 (1985).
  • Toyokuni T, Dean B, Cai SP, Boivin D, Hakomori S, Singhal AK. Synthetic vaccines – synthesis of a dimeric Tn antigen–lipopeptide conjugate that elicits immune-responses against Tn-expressing glycoproteins. J. Am. Chem. Soc.116(1), 395–396 (1994).
  • Cremer GA, Bureaud N, Piller V, Kunz H, Piller F, Delmas AF. Synthesis and biological evaluation of a multiantigenic Tn/TF-containing glycopeptide mimic of the tumor-related MUC1 glycoprotein. Chem. Med. Chem.1(9), 965–968 (2006).
  • Kaiser A, Gaidzik N, Becker T et al. Fully synthetic vaccines consisting of tumor-associated MUC1 glycopeptides and a lipopeptide ligand of the Toll-like receptor 2. Angew Chem. Int. Ed. Engl.49(21), 3688–3692 (2010).
  • Ingale S, Wolfert MA, Gaekwad J, Buskas T, Boons GJ. Robust immune responses elicited by a fully synthetic three-component vaccine. Nat. Chem. Biol.3(10), 663–667 (2007).
  • Renaudet O, BenMohamed L, Dasgupta G, Bettahi I, Dumy P. Towards a self-adjuvanting multivalent B and T cell epitope containing synthetic glycolipopeptide cancer vaccine. Chem. Med. Chem.3(5), 737–741 (2008).
  • Bettahi I, Dasgupta G, Renaudet O et al. Antitumor activity of a self-adjuvanting glyco-lipopeptide vaccine bearing B cell, CD4+ and CD8+ T cell epitopes. Cancer Immunol. Immunother.58(2), 187–200 (2009).
  • Calarese DA, Scanlan CN, Zwick MB et al. Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science300(5628), 2065–2071 (2003).
  • Wang LX, Ni J, Singh S, Li H. Binding of high-mannose-type oligosaccharides and synthetic oligomannose clusters to human antibody 2G12: implications for HIV-1 vaccine design. Chem. Biol.11(1), 127–134 (2004).
  • Li H, Wang LX. Design and synthesis of a template-assembled oligomannose cluster as an epitope mimic for human HIV-neutralizing antibody 2G12. Org. Biomol. Chem.2(4), 483–488 (2004).
  • Wang SK, Liang PH, Astronomo RD et al. Targeting the carbohydrates on HIV-1: interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN. Proc. Natl Acad. Sci. USA105(10), 3690–3695 (2008).
  • Calarese DA, Lee HK, Huang CY et al. Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12. Proc. Natl Acad. Sci. USA102(38), 13372–13377 (2005).
  • Astronomo RD, Lee HK, Scanlan CN et al. A glycoconjugate antigen based on the recognition motif of a broadly neutralizing human immunodeficiency virus antibody, 2G12, is immunogenic but elicits antibodies unable to bind to the self glycans of gp120. J. Virol.82(13), 6359–6368 (2008).
  • Krauss IJ, Joyce JG, Finnefrock AC et al. Fully synthetic carbohydrate HIV antigens designed on the logic of the 2G12 antibody. J. Am. Chem. Soc.129(36), 11042–11044 (2007).
  • Wang J, Li H, Zou G, Wang LX. Novel template-assembled oligosaccharide clusters as epitope mimics for HIV-neutralizing antibody 2G12. Design, synthesis, and antibody binding study. Org. Biomol. Chem.5(10), 1529–1540 (2007).
  • Astronomo RD, Kaltgrad E, Udit AK et al. Defining criteria for oligomannose immunogens for HIV using icosahedral virus capsid scaffolds. Chem. Biol.17(4), 357–370 (2010).
  • Stevens J, Blixt O, Paulson JC, Wilson IA. Glycan microarray technologies: tools to survey host specificity of influenza viruses. Nat. Rev. Microbiol.4(11), 857–864 (2006).
  • Wang CC, Chen JR, Tseng YC et al. Glycans on influenza hemagglutinin affect receptor binding and immune response. Proc. Natl Acad. Sci. USA106(43), 18137–18142 (2009).
  • Lin FY, Ho VA, Khiem HB et al. The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children. N. Engl. J. Med.344(17), 1263–1269 (2001).
  • Szu SC, Bystricky S, Hinojosa-Ahumada M, Egan W, Robbins JB. Synthesis and some immunologic properties of an O-acetyl pectin [poly(1→4)-α-D-GalpA]-protein conjugate as a vaccine for typhoid fever. Infect. Immun.62(12), 5545–5549 (1994).
  • Fattom AI, Horwith G, Fuller S, Propst M, Naso R. Development of StaphVAX, a polysaccharide conjugate vaccine against S. aureus infection: from the lab bench to Phase III clinical trials. Vaccine22(7), 880–887 (2004).
  • Tollersrud T, Zernichow L, Andersen SR, Kenny K, Lund A. Staphylococcus aureus capsular polysaccharide type 5 conjugate and whole cell vaccines stimulate antibody responses in cattle. Vaccine19(28–29), 3896–3903 (2001).
  • Schuerman L, Prymula R, Henckaerts I, Poolman J. ELISA IgG concentrations and opsonophagocytic activity following pneumococcal protein D conjugate vaccination and relationship to efficacy against acute otitis media. Vaccine25(11), 1962–1968 (2007).
  • Prymula R, Peeters P, Chrobok V et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet367(9512), 740–748 (2006).
  • Chapman PB, Wu D, Ragupathi G et al. Sequential immunization of melanoma patients with GD3 ganglioside vaccine and anti-idiotypic monoclonal antibody that mimics GD3 ganglioside. Clin. Cancer Res.10(14), 4717–4723 (2004).
  • Livingston PO, Adluri S, Helling F et al. Phase 1 trial of immunological adjuvant QS-21 with a GM2 ganglioside-keyhole limpet haemocyanin conjugate vaccine in patients with malignant melanoma. Vaccine12(14), 1275–1280 (1994).
  • Guthmann MD, Bitton RJ, Carnero AJ et al. Active specific immunotherapy of melanoma with a GM3 ganglioside-based vaccine: a report on safety and immunogenicity. J. Immunother.27(6), 442–451 (2004).
  • Longenecker BM, Reddish M, Koganty R, MacLean GD. Immune responses of mice and human breast cancer patients following immunization with synthetic sialyl-Tn conjugated to KLH plus detox adjuvant. Ann. NY Acad. Sci.690, 276–291 (1993).
  • MacLean GD, Reddish M, Koganty RR et al. Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus detox adjuvant. Cancer Immunol. Immunother.36(4), 215–222 (1993).
  • MacLean GD, Miles DW, Rubens RD, Reddish MA, Longenecker BM. Enhancing the effect of THERATOPE STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide. J. Immunother. Emphasis Tumor Immunol.19(4), 309–316 (1996).
  • 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. Immunother. Emphasis Tumor Immunol.19(1), 59–68 (1996).
  • Krug LM, Ragupathi G, Ng KK et al. 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 (2004).
  • Ragupathi G, Cappello S, Yi SS et al. Comparison of antibody titers after immunization with monovalent or tetravalent KLH conjugate vaccines. Vaccine20(7–8), 1030–1038 (2002).
  • Nagorny P, Kim WH, Wan Q, Lee D, Danishefsky SJ. On the emerging role of chemistry in the fashioning of biologics: synthesis of a bidomainal fucosyl gm1-based vaccine for the treatment of small cell lung cancer. J. Org. Chem.74(15), 5157–5162 (2009).
  • Kudryashov V, Glunz PW, Williams LJ, Hintermann S, Danishefsky SJ, Lloyd KO. Toward optimized carbohydrate-based anticancer vaccines: epitope clustering, carrier structure, and adjuvant all influence antibody responses to Lewis(y) conjugates in mice. Proc. Natl Acad. Sci. USA98(6), 3264–3269 (2001).
  • Buskas T, Ingale S, Boons GJ. Towards a fully synthetic carbohydrate-based anticancer vaccine: synthesis and immunological evaluation of a lipidated glycopeptide containing the tumor-associated tn antigen. Angew Chem. Int. Ed. Engl.44(37), 5985–5988 (2005).

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