Immunological Evaluation of Recent MUC1 Glycopeptide Cancer Vaccines

Md Kamal Hossain, Katherine A Wall, Md Kamal Hossain, Katherine A Wall

Abstract

Aberrantly glycosylated mucin 1 (MUC1) is a recognized tumor-specific antigen on epithelial cell tumors. A wide variety of MUC1 glycopeptide anti-cancer vaccines have been formulated by many research groups. Some researchers have used MUC1 alone as an immunogen whereas other groups used different antigenic carrier proteins such as bovine serum albumin or keyhole limpet hemocyanin for conjugation with MUC1 glycopeptide. A variety of adjuvants have been used with MUC1 glycopeptides to improve their immunogenicity. Fully synthetic multicomponent vaccines have been synthesized by incorporating different T helper cell epitopes and Toll-like receptor agonists. Some vaccine formulations utilized liposomes or nanoparticles as vaccine delivery systems. In this review, we discuss the immunological evaluation of different conjugate or synthetic MUC1 glycopeptide vaccines in different tumor or mouse models that have been published since 2012.

Keywords: BSA; KLH; MUC1; TLR; adjuvant; liposome; vaccine.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Difference between normal mucin 1 (MUC1) and tumor-associated MUC1.
Figure 2
Figure 2
Antibody-mediated antigen uptake mechanism. Anti-rhamnose antibody binding to rhamnose on the vaccine allows recognition by Fc receptor (FcR) on antigen presenting cells and enhanced uptake.

References

    1. Cheever M.A., Allison J.P., Ferris A.S., Finn O.J., Hastings B.M., Hecht T.T., Mellman I., Prindiville S.A., Viner J.L., Weiner L.M., et al. The prioritization of cancer antigens: A national cancer institute pilot project for the acceleration of translational research. Clin. Cancer Res. 2009;15:5323–5337.
    1. Cazet A., Julien S., Bobowski M., Burchell J., Delannoy P. Tumour-associated carbohydrate antigens in breast cancer. Breast Cancer Res. 2010 doi: 10.1186/bcr2577.
    1. Ju T., Cummings R.D. A unique molecular chaperone cosmc required for activity of the mammalian core 1 beta 3-galactosyltransferase. Proc. Natl. Acad. Sci. USA. 2002;99:16613–16618.
    1. Sakurai J., Hattori N., Nakajima M., Moriya T., Suzuki T., Yokoyama A., Kohno N. Differential expression of the glycosylated forms of MUC1 during lung development. Eur. J. Histochem. 2007;51:95–102.
    1. Sellers T.A., Huang Y., Cunningham J., Goode E.L., Sutphen R., Vierkant R.A., Kelemen L.E., Fredericksen Z.S., Liebow M., Pankratz V.S., et al. Association of single nucleotide polymorphisms in glycosylation genes with risk of epithelial ovarian cancer. Cancer Epidemiol. Biomark. Prev. 2008;17:397–404.
    1. Patani N., Jiang W., Mokbel K. Prognostic utility of glycosyltransferase expression in breast cancer. Cancer Genom. Proteom. 2008;5:333–340.
    1. Meany D.L., Chan D.W. Aberrant glycosylation associated with enzymes as cancer biomarkers. Clin. Proteom. 2011 doi: 10.1186/1559-0275-8-7.
    1. Wu C., Guo X., Wang W., Wang Y., Shan Y., Zhang B., Song W., Ma S., Ge J., Deng H., et al. N-acetylgalactosaminyltransferase-14 as a potential biomarker for breast cancer by immunohistochemistry. BMC Cancer. 2010 doi: 10.1186/1471-2407-10-123.
    1. Gomes J., Marcos N.T., Berois N., Osinaga E., Magalhaes A., Pinto-de-Sousa J., Almeida R., Gartner F., Reis C.A. Expression of UDP-N-acetyl-d-galactosamine: Polypeptide N-acetylgalactosaminyltransferase-6 in gastric mucosa, intestinal metaplasia, and gastric carcinoma. J. Histochem. Cytochem. 2009;57:79–86.
    1. Handerson T., Camp R., Harigopal M., Rimm D., Pawelek J. Beta1,6-branched oligosaccharides are increased in lymph node metastases and predict poor outcome in breast carcinoma. Clin. Cancer Res. 2005;11:2969–2973.
    1. Julien S., Adriaenssens E., Ottenberg K., Furlan A., Courtand G., Vercoutter-Edouart A.S., Hanisch F.G., Delannoy P., Le Bourhis X. ST6GalNAc I expression in MDA-MB-231 breast cancer cells greatly modifies their O-glycosylation pattern and enhances their tumourigenicity. Glycobiology. 2006;16:54–64.
    1. Schneider F., Kemmner W., Haensch W., Franke G., Gretschel S., Karsten U., Schlag P.M. Overexpression of sialyltransferase CMP-sialic acid:Galbeta1,3GalNAc-R alpha6-sialyltransferase is related to poor patient survival in human colorectal carcinomas. Cancer Res. 2001;61:4605–4611.
    1. Ryan S.O., Turner M.S., Gariepy J., Finn O.J. Tumor antigen epitopes interpreted by the immune system as self or abnormal-self differentially affect cancer vaccine responses. Cancer Res. 2010;70:5788–5796.
    1. Rabinovich G.A., van Kooyk Y., Cobb B.A. Glycobiology of immune responses. Ann. N. Y. Acad. Sci. 2012;1253:1–15.
    1. Tempero R.M., VanLith M.L., Morikane K., Rowse G.J., Gendler S.J., Hollingsworth M.A. CD4+ lymphocytes provide MUC1-specific tumor immunity in vivo that is undetectable in vitro and is absent in MUC1 transgenic mice. J. Immunol. 1998;161:5500–5506.
    1. Tempero R.M., Rowse G.J., Gendler S.J., Hollingsworth M.A. Passively transferred anti-MUC1 antibodies cause neither autoimmune disorders nor immunity against transplanted tumors in MUC1 transgenic mice. Int. J. Cancer. 1999;80:595–599.
    1. Von Mensdorff-Pouilly S., Petrakou E., Kenemans P., van Uffelen K., Verstraeten A.A., Snijdewint F.G., van Kamp G.J., Schol D.J., Reis C.A., Price M.R., et al. Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides and n-acetylgalactosamine (GalNAc) peptides. Int. J. Cancer. 2000;86:702–712.
    1. Soares M.M., Mehta V., Finn O.J. Three different vaccines based on the 140-amino acid MUC1 peptide with seven tandemly repeated tumor-specific epitopes elicit distinct immune effector mechanisms in wild-type versus MUC1-transgenic mice with different potential for tumor rejection. J. Immunol. 2001;166:6555–6563.
    1. Acres B., Apostolopoulos V., Balloul J.M., Wreschner D., Xing P.X., Ali-Hadji D., Bizouarne N., Kieny M.P., McKenzie I.F. MUC1-specific immune responses in human MUC1 transgenic mice immunized with various human MUC1 vaccines. Cancer Immunol. Immunother. 2000;48:588–594.
    1. Ninkovic T., Hanisch F.G. O-glycosylated human MUC1 repeats are processed in vitro by immunoproteasomes. J. Immunol. 2007;179:2380–2388.
    1. Lakshminarayanan V., Supekar N.T., Wei J., McCurry D.B., Dueck A.C., Kosiorek H.E., Trivedi P.P., Bradley J.M., Madsen C.S., Pathangey L.B., et al. MUC1 vaccines, comprised of glycosylated or non-glycosylated peptides or tumor-derived MUC1, can circumvent immunoediting to control tumor growth in MUC1 transgenic mice. PLoS ONE. 2016;11:25
    1. Barnd D.L., Lan M.S., Metzgar R.S., Finn O.J. Specific, major histocompatibility complex-unrestricted recognition of tumor-associated mucins by human cytotoxic T cells. Proc. Natl. Acad. Sci. USA. 1989;86:7159–7163.
    1. Gaidzik N., Westerlind U., Kunz H. The development of synthetic antitumour vaccines from mucin glycopeptide antigens. Chem. Soc. Rev. 2013;42:4421–4442.
    1. Palitzsch B., Hartmann S., Stergiou N., Glaffig M., Schmitt E., Kunz H. A fully synthetic four-component antitumor vaccine consisting of a mucin glycopeptide antigen combined with three different T-helper-cell epitopes. Angew. Chem. Int. Ed. Engl. 2014;53:14245–14249.
    1. Rakoff-Nahoum S., Medzhitov R. Toll-like receptors and cancer. Nat. Rev. Cancer. 2009;9:57–63.
    1. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 2005;6:345–352.
    1. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat. Rev. Immunol. 2006;6:295–307.
    1. Colombo M.P., Piconese S. Regulatory—Cell inhibition versus depletion: The right choice in cancer immunotherapy. Nat. Rev. Cancer. 2007;7:880–887.
    1. Ghiringhelli F., Puig P.E., Roux S., Parcellier A., Schmitt E., Solary E., Kroemer G., Martin F., Chauffert B., Zitvogel L. Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J. Exp. Med. 2005;202:919–929.
    1. Zhang Y., Luo F., Cai Y., Liu N., Wang L., Xu D., Chu Y. TLR1/TLR2 agonist induces tumor regression by reciprocal modulation of effector and regulatory T cells. J. Immunol. 2011;186:1963–1969.
    1. Gathuru J.K., Koide F., Ragupathi G., Adams J.L., Kerns R.T., Coleman T.P., Livingston P.O. Identification of DHBcAg as a potent carrier protein comparable to KLH for augmenting MUC1 antigenicity. Vaccine. 2005;23:4727–4733.
    1. Gilewski T., Adluri S., Ragupathi G., Zhang S., Yao T.J., Panageas K., Moynahan M., Houghton A., Norton L., Livingston P.O. Vaccination of high-risk breast cancer patients with mucin-1 (MUC1) keyhole limpet hemocyanin conjugate plus QS-21. Clin. Cancer Res. 2000;6:1693–1701.
    1. Kim S.K., Ragupathi G., Cappello S., Kagan E., Livingston P.O. Effect of immunological adjuvant combinations on the antibody and T-cell response to vaccination with MUC1-KLH and GD3-KLH conjugates. Vaccine. 2000;19:530–537.
    1. Kim S.K., Ragupathi G., Musselli C., Choi S.J., Park Y.S., Livingston P.O. Comparison of the effect of different immunological adjuvants on the antibody and T-cell response to immunization with MUC1-KLH and GD3-KLH conjugate cancer vaccines. Vaccine. 1999;18:597–603.
    1. Ragupathi G., Cappello S., Yi S.S., Canter D., Spassova M., Bornmann W.G., Danishefsky S.J., Livingston P.O. Comparison of antibody titers after immunization with monovalent or tetravalent KLH conjugate vaccines. Vaccine. 2002;20:1030–1038.
    1. Cai H., Huang Z.H., Shi L., Sun Z.Y., Zhao Y.F., Kunz H., Li Y.M. Variation of the glycosylation pattern in MUC1 glycopeptide BSA vaccines and its influence on the immune response. Angew. Chem. Int. Ed. Engl. 2012;51:1719–1723.
    1. Hoffmann-Roder A., Johannes M. Synthesis of a MUC1-glycopeptide-BSA conjugate vaccine bearing the 3′-deoxy-3′-fluoro-Thomsen-Friedenreich antigen. Chem. Commun. (Camb.) 2011;47:9903–9905.
    1. Hoffmann-Roder A., Kaiser A., Wagner S., Gaidzik N., Kowalczyk D., Westerlind U., Gerlitzki B., Schmitt E., Kunz H. Synthetic antitumor vaccines from tetanus toxoid conjugates of MUC1 glycopeptides with the Thomsen-Friedenreich antigen and a fluorine-substituted analogue. Angew. Chem. Int. Ed. Engl. 2010;49:8498–8503.
    1. Fang F., Ma J., Ni W., Wang F., Sun X., Li Y., Li Q., Xie F., Wang J., Zhai R., et al. MUC1 and maltosebinding protein recombinant fusion protein combined with Bacillus Calmette-Guerin induces MUC1 specific and nonspecific antitumor immunity in mice. Mol. Med. Rep. 2014;10:1056–1064.
    1. Yuan S., Shi C., Ling R., Wang T., Wang H., Han W. Immunization with two recombinant Bacillus Calmette-Guerin vaccines that combine the expression of multiple tandem repeats of mucin-1 and colony stimulating-factor suppress breast tumor growth in mice. J. Cancer Res. Clin. Oncol. 2010;136:1359–1367.
    1. Yuan S., Shi C., Liu L., Han W. MUC1-based recombinant Bacillus Calmette-Guerin vaccines as candidates for breast cancer immunotherapy. Expert Opin. Biol. Ther. 2010;10:1037–1048.
    1. Wang Y., Liu C., Xia Q., Wang P., Li B., Lu Z., Sun J., Wu H., Yu B., Wu J., et al. Antitumor effect of adenoviral vector prime protein boost immunity targeting the MUC1 VNTRs. Oncol. Rep. 2014;31:1437–1444.
    1. Lu W., Qiu L., Yan Z., Lin Z., Cao M., Hu C., Wang Z., Wang J., Yu Y., Cheng X., et al. Cytotoxic T cell responses are enhanced by antigen design involving the presentation of MUC1 peptide on cholera toxin B subunit. Oncotarget. 2015;6:34537–34548.
    1. Kimura T., Finn O.J. MUC1 immunotherapy is here to stay. Expert Opin. Biol. Ther. 2013;13:35–49.
    1. Cai H., Huang Z.-H., Shi L., Zou P., Zhao Y.-F., Kunz H., Li Y.-M. Synthesis of Tn/T antigen MUC1 glycopeptide BSA conjugates and their evaluation as vaccines. Eur. J. Org. Chem. 2011;2011:3685–3689.
    1. Dziadek S., Kowalczyk D., Kunz H. Synthetic vaccines consisting of tumor-associated MUC1 glycopeptide antigens and bovine serum albumin. Angew. Chem. Int. Ed. Engl. 2005;44:7624–7630.
    1. Cai H., Chen M.S., Sun Z.Y., Zhao Y.F., Kunz H., Li Y.M. Self-adjuvanting synthetic antitumor vaccines from MUC1 glycopeptides conjugated to T-cell epitopes from tetanus toxoid. Angew. Chem. Int. Ed. Engl. 2013;52:6106–6110.
    1. Broderson J.R. A retrospective review of lesions associated with the use of Freund’s adjuvant. Lab. Anim. Sci. 1989;39:400–405.
    1. Johannes M., Reindl M., Gerlitzki B., Schmitt E., Hoffmann-Roder A. Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen-Friedenreich epitope. Beilstein J. Org. Chem. 2015;11:155–161.
    1. Ragupathi G., Koide F., Livingston P.O., Cho Y.S., Endo A., Wan Q., Spassova M.K., Keding S.J., Allen J., Ouerfelli O., 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. 2006;128:2715–2725.
    1. Zhu J., Wan Q., Lee D., Yang G., Spassova M.K., Ouerfelli O., Ragupathi G., Damani P., Livingston P.O., Danishefsky S.J. From synthesis to biologics: Preclinical data on a chemistry derived anticancer vaccine. J. Am. Chem. Soc. 2009;131:9298–9303.
    1. Kaiser A., Gaidzik N., Westerlind U., Kowalczyk D., Hobel A., Schmitt E., Kunz H. A synthetic vaccine consisting of a tumor-associated sialyl-T(n)-MUC1 tandem-repeat glycopeptide and tetanus toxoid: Induction of a strong and highly selective immune response. Angew. Chem. Int. Ed. Engl. 2009;48:7551–7555.
    1. Palitzsch B., Gaidzik N., Stergiou N., Stahn S., Hartmann S., Gerlitzki B., Teusch N., Flemming P., Schmitt E., Kunz H. A synthetic glycopeptide vaccine for the induction of a monoclonal antibody that differentiates between normal and tumor mammary cells and enables the diagnosis of human pancreatic cancer. Angew. Chem. Int. Ed. Engl. 2016;55:2894–2898.
    1. Buskas T., Li Y., Boons G.J. The immunogenicity of the tumor-associated antigen Lewis(y) may be suppressed by a bifunctional cross-linker required for coupling to a carrier protein. Chemistry. 2004;10:3517–3524.
    1. Herzenberg L.A., Tokuhisa T., Herzenberg L.A. Carrier-priming leads to hapten-specific suppression. Nature. 1980;285:664–667.
    1. Kagan E., Ragupathi G., Yi S.S., Reis C.A., Gildersleeve J., Kahne D., Clausen H., Danishefsky S.J., Livingston P.O. Comparison of antigen constructs and carrier molecules for augmenting the immunogenicity of the monosaccharide epithelial cancer antigen Tn. Cancer Immunol. Immunother. 2005;54:424–430.
    1. Schutze M.P., Leclerc C., Jolivet M., Audibert F., Chedid L. Carrier-induced epitopic suppression, a major issue for future synthetic vaccines. J. Immunol. 1985;135:2319–2322.
    1. Cai H., Sun Z.Y., Chen M.S., Zhao Y.F., Kunz H., Li Y.M. Synthetic multivalent glycopeptide-lipopeptide antitumor vaccines: Impact of the cluster effect on the killing of tumor cells. Angew. Chem. Int. Ed. Engl. 2014;53:1699–1703.
    1. Geraci C., Consoli G.M., Granata G., Galante E., Palmigiano A., Pappalardo M., Di Puma S.D., Spadaro A. First self-adjuvant multicomponent potential vaccine candidates by tethering of four or eight MUC1 antigenic immunodominant PDTRP units on a calixarene platform: Synthesis and biological evaluation. Bioconjug. Chem. 2013;24:1710–1720.
    1. McDonald D.M., Wilkinson B.L., Corcilius L., Thaysen-Andersen M., Byrne S.N., Payne R.J. Synthesis and immunological evaluation of self-adjuvanting MUC1-macrophage activating lipopeptide 2 conjugate vaccine candidates. Chem. Commun. (Camb.) 2014;50:10273–10276.
    1. Borsutzky S., Kretschmer K., Becker P.D., Muhlradt P.F., Kirschning C.J., Weiss S., Guzman C.A. The mucosal adjuvant macrophage-activating lipopeptide-2 directly stimulates B lymphocytes via the TLR2 without the need of accessory cells. J. Immunol. 2005;174:6308–6313.
    1. Nicholls E.F., Madera L., Hancock R.E. Immunomodulators as adjuvants for vaccines and antimicrobial therapy. Ann. N. Y. Acad. Sci. 2010;1213:46–61.
    1. Korsholm K.S., Agger E.M., Foged C., Christensen D., Dietrich J., Andersen C.S., Geisler C., Andersen P. The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes. Immunology. 2007;121:216–226.
    1. Persing D.H., Coler R.N., Lacy M.J., Johnson D.A., Baldridge J.R., Hershberg R.M., Reed S.G. Taking toll: Lipid A mimetics as adjuvants and immunomodulators. Trends Microbiol. 2002;10:S32–S37.
    1. Takeuchi O., Hoshino K., Kawai T., Sanjo H., Takada H., Ogawa T., Takeda K., Akira S. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity. 1999;11:443–451.
    1. Yang M., Yan Y., Fang M., Wan M., Wu X., Zhang X., Zhao T., Wei H., Song D., Wang L., et al. MF59 formulated with CpG ODN as a potent adjuvant of recombinant hsp65-MUC1 for inducing anti-MUC1+ tumor immunity in mice. Int. Immunopharmacol. 2012;13:408–416.
    1. Lakshminarayanan V., Thompson P., Wolfert M.A., Buskas T., Bradley J.M., Pathangey L.B., Madsen C.S., Cohen P.A., Gendler S.J., Boons G.J. Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine. Proc. Natl. Acad. Sci. USA. 2012;109:261–266.
    1. Abdel-Aal A.B., Lakshminarayanan V., Thompson P., Supekar N., Bradley J.M., Wolfert M.A., Cohen P.A., Gendler S.J., Boons G.J. Immune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonist. Chembiochem. 2014;15:1508–1513.
    1. Thompson P., Lakshminarayanan V., Supekar N.T., Bradley J.M., Cohen P.A., Wolfert M.A., Gendler S.J., Boons G.J. Linear synthesis and immunological properties of a fully synthetic vaccine candidate containing a sialylated MUC1 glycopeptide. Chem. Commun. (Camb.) 2015;51:10214–10217.
    1. Cai H., Degliangeli F., Palitzsch B., Gerlitzki B., Kunz H., Schmitt E., Fiammengo R., Westerlind U. Glycopeptide-functionalized gold nanoparticles for antibody induction against the tumor associated mucin-1 glycoprotein. Bioorg. Med. Chem. 2016;24:1132–1135.
    1. Sarkar S., Lombardo S.A., Herner D.N., Talan R.S., Wall K.A., Sucheck S.J. Synthesis of a single-molecule L-rhamnose-containing three-component vaccine and evaluation of antigenicity in the presence of anti-L-rhamnose antibodies. J. Am. Chem. Soc. 2010;132:17236–17246.
    1. Sarkar S., Salyer A.C., Wall K.A., Sucheck S.J. Synthesis and immunological evaluation of a MUC1 glycopeptide incorporated into L-rhamnose displaying liposomes. Bioconjug. Chem. 2013;24:363–375.
    1. Karmakar P., Lee K., Sarkar S., Wall K.A., Sucheck S.J. Synthesis of a liposomal MUC1 glycopeptide-based immunotherapeutic and evaluation of the effect of L-rhamnose targeting on cellular immune responses. Bioconjug. Chem. 2016;27:110–120.
    1. Hartmann S., Nuhn L., Palitzsch B., Glaffig M., Stergiou N., Gerlitzki B., Schmitt E., Kunz H., Zentel R. CpG-loaded multifunctional cationic nanohydrogel particles as self-adjuvanting glycopeptide antitumor vaccines. Adv. Healthc. Mater. 2015;4:522–527.
    1. Nuhn L., Hartmann S., Palitzsch B., Gerlitzki B., Schmitt E., Zentel R., Kunz H. Water-soluble polymers coupled with glycopeptide antigens and T-cell epitopes as potential antitumor vaccines. Angew. Chem. Int. Ed. Engl. 2013;52:10652–10656.
    1. Glaffig M., Palitzsch B., Stergiou N., Schull C., Strassburger D., Schmitt E., Frey H., Kunz H. Enhanced immunogenicity of multivalent MUC1 glycopeptide antitumour vaccines based on hyperbranched polymers. Org. Biomol. Chem. 2015;13:10150–10154.
    1. Huang Z.H., Shi L., Ma J.W., Sun Z.Y., Cai H., Chen Y.X., Zhao Y.F., Li Y.M. A totally synthetic, self-assembling, adjuvant-free MUC1 glycopeptide vaccine for cancer therapy. J. Am. Chem. Soc. 2012;134:8730–8733.
    1. Mond J.J., Lees A., Snapper C.M. T cell-independent antigens type 2. Annu. Rev. Immunol. 1995;13:655–692.
    1. Liu Y.F., Sun Z.Y., Chen P.G., Huang Z.H., Gao Y., Shi L., Zhao Y.F., Chen Y.X., Li Y.M. Glycopeptide nanoconjugates based on multilayer self-assembly as an antitumor vaccine. Bioconjug. Chem. 2015;26:1439–1442.
    1. Pillai K., Pourgholami M.H., Chua T.C., Morris D.L. MUC1 as a potential target in anticancer therapies. Am. J. Clin. Oncol. 2015;38:108–118.
    1. Weng Y., Shao L., Ouyang H., Liu Y., Yao J., Yang H., Luo Y., Wang H., Zhao Z., Mou H., et al. A unique MUC1–2-VNTR DNA vaccine suppresses tumor growth and prolongs survival in a murine multiple myeloma model. Oncol. Rep. 2012;27:1815–1822.
    1. Richichi B., Thomas B., Fiore M., Bosco R., Qureshi H., Nativi C., Renaudet O., BenMohamed L. A cancer therapeutic vaccine based on clustered Tn-antigen mimetics induces strong antibody-mediated protective immunity. Angew. Chem. Int. Ed. Engl. 2014;53:11917–11920.
    1. Nativi C., Renaudet O. Recent progress in antitumoral synthetic vaccines. ACS Med. Chem. Lett. 2014;5:1176–1178.
    1. Yang F., Zheng X.J., Huo C.X., Wang Y., Zhang Y., Ye X.S. Enhancement of the immunogenicity of synthetic carbohydrate vaccines by chemical modifications of STn antigen. ACS Chem. Biol. 2011;6:252–259.
    1. Yin Z., Huang X. Recent development in carbohydrate based anti-cancer vaccines. J. Carbohydr. Chem. 2012;31:143–186.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi