Structure-based Design of Anti-cancer Vaccines: The Significance of
Antigen Presentation to Boost the Immune Response

Alicia      Asín; Fayna      García-Martín; Jesús   Hector    Busto; Alberto      Avenoza; Jesús   Manuel   Peregrina; Francisco      Corzana
doi:10.2174/0929867328666210810152917
Abstract

Immunotherapy, alone or in combination with other therapies, is widely used against cancer. Glycoprotein Mucin 1 (MUC1), which is overexpressed and aberrantly glycosylated in tumor cells, is one of the most promising candidates to engineer new cancer vaccines. In this context, the development of stable antigens that can elicit a robust immune response is mandatory. Here, we describe the design and in vivo biological evaluation of three vaccine candidates based on MUC1 glycopeptides that comprise unnatural elements in their structure. By placing the Tn antigen (GalNAcα-O-Ser/Thr) at the center of the design, the chemical modifications include changes to the peptide backbone, glycosidic linkage, and carbohydrate level. Significantly, the three vaccines elicit robust immune responses in mice and produce antibodies that can be recognized by several human cancer cells. In all cases, a link was established between the conformational changes induced by the new elements in the antigen presentation and the immune response induced in mice. According to our data, the development of effective MUC1-based vaccines should use surrogates that mimic the conformational space of aberrantly glycosylated MUC1 glycopeptides found in tumors.
Keywords: Cancer vaccine, immunotherapy, mucin, glycopeptide structure, non-natural antigens, tumor-associated carbohydrates, Tn antigen.
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[1] 
Anderson, R.M. The impact of vaccination on the epidemiology of infectious diseases. In: The Vaccine Book; Second Edition. , 2016. 
[http://dx.doi.org/10.1016/B978-0-12-802174-3.00001-1] 
[2] 
Hollingsworth, R.E.; Jansen, K. Turning the corner on therapeutic cancer vaccines. NPJ Vaccines.,  2019, 4, 7.
[http://dx.doi.org/10.1038/s41541-019-0103-y] [PMID:  30774998] 
[3] 
Guo, C.; Manjili, M.H.; Subjeck, J.R.; Sarkar, D.; Fisher, P.B.; Wang, X.Y. Therapeutic cancer vaccines: past, present, and future. Adv. Cancer Res.,  2013, 119, 421-475.
[http://dx.doi.org/10.1016/B978-0-12-407190-2.00007-1] [PMID:  23870514] 
[4] 
Rezaei, N. Tumor Antigens. Vaccines for Cancer Immunotherapy: An Evidence-Based Review on Current Status and Future Perspectives. Indian J. Med. Res.,  2019, 150(5), 514.
[http://dx.doi.org/10.4103/ijmr.IJMR_1275_19] 
[5] 
Waldman, A.D.; Fritz, J.M.; Lenardo, M.J. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunol.,  2020, 20(11), 651-668.
[http://dx.doi.org/10.1038/s41577-020-0306-5] [PMID:  32433532] 
[6] 
Lewis, J.J.; Houghton, A.N. Definition of tumor antigens suitable for vaccine construction. Semin. Cancer Biol.,  1995, 6(6), 321-327.
[http://dx.doi.org/10.1016/1044-579X(95)90001-2] [PMID:  8938270] 
[7] 
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.; Matrisian, L.M. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin. Cancer Res.,  2009, 15(17), 5323-5337.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-0737] [PMID:  19723653] 
[8] 
Taylor-Papadimitriou, J.; Burchell, J.; Miles, D.W.; Dalziel, M. MUC1 and cancer. Biochim. Biophys. Acta,  1999, 1455(2-3), 301-313.
[http://dx.doi.org/10.1016/S0925-4439(99)00055-1] [PMID:  10571020] 
[9] 
Gill, D.J.; Clausen, H.; Bard, F. Location, location, location: new insights into O-GalNAc protein glycosylation. Trends Cell Biol.,  2011, 21(3), 149-158.
[http://dx.doi.org/10.1016/j.tcb.2010.11.004] [PMID:  21145746] 
[10] 
Kudelka, M.R.; Ju, T.; Heimburg-Molinaro, J.; Cummings, R.D. Simple sugars to complex disease mucin-type O-glycans in cancer. Adv. Cancer Res.,  2015, 126, 53-135.
[http://dx.doi.org/10.1016/bs.acr.2014.11.002] [PMID:  25727146] 
[11] 
Beckwith, D.M.; Cudic, M. Tumor-associated O-glycans of MUC1: Carriers of the glyco-code and targets for cancer vaccine design. Semin. Immunol.,  2020, 47, 101389.
[http://dx.doi.org/10.1016/j.smim.2020.101389] [PMID:  31926647] 
[12] 
Chia, J.; Goh, G.; Bard, F. Short O-GalNAc glycans: regulation and role in tumor development and clinical perspectives. Biochim. Biophys. Acta,  2016, 1860(8), 1623-1639.
[http://dx.doi.org/10.1016/j.bbagen.2016.03.008] [PMID:  26968459] 
[13] 
Büll, C.; Stoel, M.A.; den Brok, M.H.; Adema, G.J. Sialic acids sweeten a tumor’s life. Cancer Res.,  2014, 74(12), 3199-3204.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0728] [PMID:  24830719] 
[14] 
Price, M.R.; Rye, P.D.; Petrakou, E.; Murray, A.; Brady, K.; Imai, S.; Haga, S.; Kiyozuka, Y.; Schol, D.; Meulenbroek, M.F.A.; Snijdewint, F.G.M.; von Mensdorff-Pouilly, S.; Verstraeten, R.A.; Kenemans, P.; Blockzjil, A.; Nilsson, K.; Nilsson, O.; Reddish, M.; Suresh, M.R.; Koganty, R.R.; Fortier, S.; Baronic, L.; Berg, A.; Longenecker, M.B.; Hilgers, J.; Boer, M.; Karanikas, V.; McKenzie, I.F.C.; Galanina, O.E.; Simeoni, L.A.; Ter-Grigoryan, A.G.; Belyanchikov, I.M.; Bovin, N.V.; Cao, Y.; Karsten, U.; Dai, J.; Allard, W.J.; Davis, G.; Yeung, K.K.; Hanisch, F.G.; Lloyd, K.O.; Kudryashov, V.; Sikut, R.; Sikut, A.; Zhang, K.; Baeckström, D.; Hansson, G.C.; Reis, C.A.; Hassan, H.; Bennett, E.P.; Claussen, H.; Norum, L.; Varaas, T.; Kierulf, B.; Nustad, K.; Ciborowski, P.; Konitzki, W.M.; Magarian-Blander, J.; Finn, O.J.; Hilgers, J. Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin. San Diego, Calif., November 17-23, 1996. Tumour Biol.,  1998, 19(Suppl. 1), 1-20.
[http://dx.doi.org/10.1159/000056500] [PMID:  9422084] 
[15] 
Lloyd, K.O.; Burchell, J.; Kudryashov, V.; Yin, B.W.T.; Taylor-Papadimitriou, J. Comparison of O-linked carbohydrate chains in MUC-1 mucin from normal breast epithelial cell lines and breast carcinoma cell lines. Demonstration of simpler and fewer glycan chains in tumor cells. J. Biol. Chem.,  1996, 271(52), 33325-33334.
[http://dx.doi.org/10.1074/jbc.271.52.33325] [PMID:  8969192] 
[16] 
Feng, D.; Shaikh, A.S.; Wang, F. Recent Advance in Tumor-associated Carbohydrate Antigens (TACAs)-based Antitumor Vaccines. ACS Chem. Biol.,  2016, 11(4), 850-863.
[http://dx.doi.org/10.1021/acschembio.6b00084] [PMID:  26895482] 
[17] 
Martínez-Sáez, N.; Peregrina, J.M.; Corzana, F. Principles of mucin structure: implications for the rational design of cancer vaccines derived from MUC1-glycopeptides. Chem. Soc. Rev.,  2017, 46(23), 7154-7175.
[http://dx.doi.org/10.1039/C6CS00858E] [PMID:  29022615] 
[18] 
Wilson, R.M.; Danishefsky, S.J. A vision for vaccines built from fully synthetic tumor-associated antigens: from the laboratory to the clinic. J. Am. Chem. Soc.,  2013, 135(39), 14462-14472.
[http://dx.doi.org/10.1021/ja405932r] [PMID:  23944352] 
[19] 
Gaidzik, N.; Westerlind, U.; Kunz, H. The development of synthetic antitumour vaccines from mucin glycopeptide antigens. Chem. Soc. Rev.,  2013, 42(10), 4421-4442.
[http://dx.doi.org/10.1039/c3cs35470a] [PMID:  23440054] 
[20] 
Buskas, T.; Thompson, P.; Boons, G.J. Immunotherapy for cancer: synthetic carbohydrate-based vaccines. Chem. Commun.,  2009, (36), 5335-5349.
[http://dx.doi.org/10.1039/b908664c] [PMID:  19724783] 
[21] 
Wolfert, M.A.A.; Boons, G.J. Adaptive immune activation: glycosylation does matter. Nat. Chem. Biol.,  2013, 9(12), 776-784.
[http://dx.doi.org/10.1038/nchembio.1403] [PMID:  24231619] 
[22] 
Li, W.H.; Li, Y.M. Chemical Strategies to Boost Cancer Vaccines. Chem. Rev.,  2020, 120(20), 11420-11478.
[http://dx.doi.org/10.1021/acs.chemrev.9b00833] [PMID:  32914967] 
[23] 
Mettu, R.; Chen, C-Y.; Wu, C-Y. Synthetic carbohydrate-based vaccines: challenges and opportunities. J. Biomed. Sci.,  2020, 27(1), 9.
[http://dx.doi.org/10.1186/s12929-019-0591-0] [PMID:  31900143] 
[24] 
Gao, T.; Cen, Q.; Lei, H. A review on development of MUC1-based cancer vaccine. Biomed. Pharmacother.,  2020, 132110888
[http://dx.doi.org/10.1016/j.biopha.2020.110888] [PMID:  33113416] 
[25] 
Miles, D.; Roché, H.; Martin, M.; Perren, T.J.; Cameron, D.A.; Glaspy, J.; Dodwell, D.; Parker, J.; Mayordomo, J.; Tres, A.; Murray, J.L.; Ibrahim, N.K. Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer. Oncologist,  2011, 16(8), 1092-1100.
[http://dx.doi.org/10.1634/theoncologist.2010-0307] [PMID:  21572124] 
[26] 
Slingluff, C.L., Jr The present and future of peptide vaccines for cancer: single or multiple, long or short, alone or in combination? Cancer J.,  2011, 17(5), 343-350.
[http://dx.doi.org/10.1097/PPO.0b013e318233e5b2] [PMID:  21952285] 
[27] 
Purcell, A.W.; McCluskey, J.; Rossjohn, J. More than one reason to rethink the use of peptides in vaccine design. Nat. Rev. Drug Discov.,  2007, 6(5), 404-414.
[http://dx.doi.org/10.1038/nrd2224] [PMID:  17473845] 
[28] 
Katsara, M.; Minigo, G.; Plebanski, M.; Apostolopoulos, V. The good, the bad and the ugly: how altered peptide ligands modulate immunity. Expert Opin. Biol. Ther.,  2008, 8(12), 1873-1884.
[http://dx.doi.org/10.1517/14712590802494501] [PMID:  18990075] 
[29] 
Webb, A.I.; Aguilar, M.I.; Purcell, A.W. Optimisation of peptide-based cytotoxic t-cell determinants using non-natural amino acids. Lett. Pept. Sci.,  2003, 10, 561-569.
[http://dx.doi.org/10.1007/BF02442589] 
[30] 
Hoppes, R.; Oostvogels, R.; Luimstra, J.J.; Wals, K.; Toebes, M.; Bies, L.; Ekkebus, R.; Rijal, P.; Celie, P.H.N.; Huang, J.H.; Emmelot, M.E.; Spaapen, R.M.; Lokhorst, H.; Schumacher, T.N.M.; Mutis, T.; Rodenko, B.; Ovaa, H. Altered peptide ligands revisited: vaccine design through chemically modified HLA-A2-restricted T cell epitopes. J. Immunol.,  2014, 193(10), 4803-4813.
[http://dx.doi.org/10.4049/jimmunol.1400800] [PMID:  25311806] 
[31] 
Pifferi, C.; Berthet, N.; Renaudet, O. Cyclopeptide scaffolds in carbohydrate-based synthetic vaccines. Biomater. Sci.,  2017, 5(5), 953-965.
[http://dx.doi.org/10.1039/C7BM00072C] [PMID:  28275765] 
[32] 
Pifferi, C.; Ruiz-de-Angulo, A.; Goyard, D.; Tiertant, C.; Sacristán, N.; Barriales, D.; Berthet, N.; Anguita, J.; Renaudet, O.; Fernández-Tejada, A. Chemical synthesis and immunological evaluation of new generation multivalent anticancer vaccines based on a Tn antigen analogue. Chem. Sci.,  2020, 11(17), 4488-4498.
[http://dx.doi.org/10.1039/D0SC00544D] [PMID:  34122907] 
[33] 
Vichier-Guerre, S.; Lo-Man, R.; Huteau, V.; Dériaud, E.; Leclerc, C.; Bay, S. Synthesis and immunological evaluation of an antitumor neoglycopeptide vaccine bearing a novel homoserine Tn antigen. Bioorg. Med. Chem. Lett.,  2004, 14(13), 3567-3570.
[http://dx.doi.org/10.1016/j.bmcl.2004.04.047] [PMID:  15177475] 
[34] 
Nativi, C.; Papi, F.; Roelens, S. Tn antigen analogues: the synthetic way to “upgrade” an attracting tumour associated carbohydrate antigen (TACA). Chem. Commun.,  2019, 55(54), 7729-7736.
[http://dx.doi.org/10.1039/C9CC02920F] [PMID:  31225574] 
[35] 
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(44), 11917-11920.
[http://dx.doi.org/10.1002/anie.201406897] [PMID:  25168881] 
[36] 
Amedei, A.; Asadzadeh, F.; Papi, F.; Vannucchi, M. G.; Ferrucci, V.; Bermejo, I. A.; Fragai, M.; De Almeida, C. V.; Cerofolini, L.; Giuntini, S.; Bombaci, M.; Pesce, E.; Niccolai, E.; Natali, F.; Guarini, E.; Gabel, F.; Traini, C.; Catarinicchia, S.; Ricci, F.; Orzalesi, L.; Berti, F.; Corzana, F.; Zollo, M.; Grifantini, R.; Nativi, C. A Structurally simple vaccine candidate reduces progression and dissemination of triple-negative breast cancer. iScience,  2020, 23, 101250.
[http://dx.doi.org/10.1016/j.isci.2020.101250] 
[37] 
Awad, L.; Madani, R.; Gillig, A.; Kolympadi, M.; Philgren, M.; Muhs, A.; Gérard, C.; Vogel, P. A C-linked disaccharide analogue of Thomsen-Friedenreich epitope induces a strong immune response in mice. Chemistry,  2012, 18(28), 8578-8582.
[http://dx.doi.org/10.1002/chem.201200364] [PMID:  22692824] 
[38] 
Bundle, D.R.; Rich, J.R.; Jacques, S.; Yu, H.N.; Nitz, M.; Ling, C-C. Thiooligosaccharide conjugate vaccines evoke antibodies specific for native antigens. Angew. Chem. Int. Ed. Engl.,  2005, 44(47), 7725-7729.
[http://dx.doi.org/10.1002/anie.200502179] [PMID:  16276545] 
[39] 
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(3), 252-259.
[http://dx.doi.org/10.1021/cb100287q] [PMID:  21121644] 
[40] 
Song, C.; Zheng, X.J.; Guo, H.; Cao, Y.; Zhang, F.; Li, Q.; Ye, X.S.; Zhou, Y. Fluorine-modified sialyl-Tn-CRM197 vaccine elicits a robust immune response. Glycoconj. J.,  2019, 36(5), 399-408.
[http://dx.doi.org/10.1007/s10719-019-09884-0] [PMID:  31267246] 
[41] 
Hoffmann-Röder, 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(45), 8498-8503.
[http://dx.doi.org/10.1002/anie.201003810] [PMID:  20878823] 
[42] 
Oberbillig, T.; Mersch, C.; Wagner, S.; Hoffmann-Röder, A. Antibody recognition of fluorinated MUC1 glycopeptide antigens. Chem. Commun.,  2012, 48(10), 1487-1489.
[http://dx.doi.org/10.1039/C1CC15139H] [PMID:  21986937] 
[43] 
Corzana, F.; Busto, J.H.; Jiménez-Osés, G.; Asensio, J.L.; Jiménez-Barbero, J.; Peregrina, J.M.; Avenoza, A. New insights into α-GalNAc-Ser motif: influence of hydrogen bonding versus solvent interactions on the preferred conformation. J. Am. Chem. Soc.,  2006, 128(45), 14640-14648.
[http://dx.doi.org/10.1021/ja064539u] [PMID:  17090050] 
[44] 
Corzana, F.; Busto, J.H.; Jiménez-Osés, G.; García de Luis, M.; Asensio, J.L.; Jiménez-Barbero, J.; Peregrina, J.M.; Avenoza, A. Serine versus threonine glycosylation: the methyl group causes a drastic alteration on the carbohydrate orientation and on the surrounding water shell. J. Am. Chem. Soc.,  2007, 129(30), 9458-9467.
[http://dx.doi.org/10.1021/ja072181b] [PMID:  17616194] 
[45] 
Coltart, D.M.; Royyuru, A.K.; Williams, L.J.; Glunz, P.W.; Sames, D.; Kuduk, S.D.; Schwarz, J.B.; Chen, X.T.; Danishefsky, S.J.; Live, D.H. Principles of mucin architecture: structural studies on synthetic glycopeptides bearing clustered mono-, di-, tri-, and hexasaccharide glycodomains. J. Am. Chem. Soc.,  2002, 124(33), 9833-9844.
[http://dx.doi.org/10.1021/ja020208f] [PMID:  12175243] 
[46] 
Bermejo, I.A.; Usabiaga, I.; Compañón, I.; Castro-López, J.; Insausti, A.; Fernández, J.A.; Avenoza, A.; Busto, J.H.; Jiménez-Barbero, J.; Asensio, J.L.; Peregrina, J.M.; Jiménez-Osés, G.; Hurtado-Guerrero, R.; Cocinero, E.J.; Corzana, F. Water sculpts the distinctive shapes and dynamics of the tumor-associated carbohydrate Tn antigens: implications for their molecular recognition. J. Am. Chem. Soc.,  2018, 140(31), 9952-9960.
[http://dx.doi.org/10.1021/jacs.8b04801] [PMID:  30004703] 
[47] 
Compañón, I.; Guerreiro, A.; Mangini, V.; Castro-López, J.; Escudero-Casao, M.; Avenoza, A.; Busto, J.H.; Castillón, S.; Jiménez-Barbero, J.; Asensio, J.L.; Jiménez-Osés, G.; Boutureira, O.; Peregrina, J.M.; Hurtado-Guerrero, R.; Fiammengo, R.; Bernardes, G.J.L.; Corzana, F. Structure-based design of potent tumor-associated antigens: modulation of peptide presentation by single-atom O/S or O/Se substitutions at the glycosidic linkage. J. Am. Chem. Soc.,  2019, 141(9), 4063-4072.
[http://dx.doi.org/10.1021/jacs.8b13503] [PMID:  30726084] 
[48] 
Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J.M.; Sucunza, D.; Zurbano, M.M. Enantioselective Synthesis of (S)- and (R)-α-Methylserines: Application to the Synthesis of (S)- and (R)-N-Boc-N,O-Isopropylidene-α-methylseri-nals. Tetrahedron Asymmetry,  2001, 12, 949-957.
[http://dx.doi.org/10.1016/S0957-4166(01)00159-8] 
[49] 
Aydillo, C.; Jiménez-Osés, G.; Busto, J.H.; Peregrina, J.M.; Zurbano, M.M.; Avenoza, A. Theoretical evidence for pyramidalized bicyclic serine enolates in highly diastereoselective alkylations. Chem. Eur. J.,  2007, 13(17), 4840-4848.
[http://dx.doi.org/10.1002/chem.200601746] [PMID:  17366514] 
[50] 
Corzana, F.; Busto, J.H.; Marcelo, F.; de Luis, M.G.; Asensio, J.L.; Martín-Santamaría, S.; Sáenz, Y.; Torres, C.; Jiménez-Barbero, J.; Avenoza, A.; Peregrina, J.M. Rational design of a Tn antigen mimic. Chem. Commun.,  2011, 47(18), 5319-5321.
[http://dx.doi.org/10.1039/c1cc10192g] [PMID:  21451866] 
[51] 
Martínez-Sáez, N.; Supekar, N.T.; Wolfert, M.A.; Bermejo, I.A.; Hurtado-Guerrero, R.; Asensio, J.L.; Jiménez-Barbero, J.; Busto, J.H.; Avenoza, A.; Boons, G-J.; Peregrina, J.M.; Corzana, F. Mucin architecture behind the immune response: design, evaluation and conformational analysis of an antitumor vaccine derived from an unnatural MUC1 fragment. Chem. Sci.,  2016, 7(3), 2294-2301.
[http://dx.doi.org/10.1039/C5SC04039F] [PMID:  29910919] 
[52] 
Demizu, Y.; Doi, M.; Kurihara, M.; Okuda, H.; Nagano, M.; Suemune, H.; Tanaka, M. Conformational studies on peptides containing α,α-disubstituted α-amino acids: chiral cyclic α,α-disubstituted α-amino acid as an α-helical inducer. Org. Biomol. Chem.,  2011, 9(9), 3303-3312.
[http://dx.doi.org/10.1039/c0ob01146k] [PMID:  21437330] 
[53] 
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(1), 261-266.
[http://dx.doi.org/10.1073/pnas.1115166109] [PMID:  22171012] 
[54] 
Martínez-Sáez, N.; Castro-López, J.; Valero-González, J.; Madariaga, D.; Compañón, I.; Somovilla, V.J.; Salvadó, M.; Asensio, J.L.; Jiménez-Barbero, J.; Avenoza, A.; Busto, J.H.; Bernardes, G.J.L.; Peregrina, J.M.; Hurtado-Guerrero, R.; Corzana, F. Deciphering the non-equivalence of serine and threonine O-glycosylation points: implications for molecular recognition of the tn antigen by an anti-MUC1 antibody. Angew. Chem. Int. Ed. Engl.,  2015, 54(34), 9830-9834.
[http://dx.doi.org/10.1002/anie.201502813] [PMID:  26118689] 
[55] 
Jiménez-Moreno, E.; Gómez, A.M.; Bastida, A.; Corzana, F.; Jiménez-Oses, G.; Jiménez-Barbero, J.; Asensio, J.L. Modulating weak interactions for molecular recognition: a dynamic combinatorial analysis for assessing the contribution of electrostatics to the stability of CH-π bonds in water. Angew. Chem. Int. Ed. Engl.,  2015, 54(14), 4344-4348.
[http://dx.doi.org/10.1002/anie.201411733] [PMID:  25664754] 
[56] 
Jiménez-Moreno, E.; Jiménez-Osés, G.; Gómez, A.M.; Santana, A.G.; Corzana, F.; Bastida, A.; Jiménez-Barbero, J.; Asensio, J.L. A thorough experimental study of CH/π interactions in water: quantitative structure-stability relationships for carbohydrate/aromatic complexes. Chem. Sci.,  2015, 6(11), 6076-6085.
[http://dx.doi.org/10.1039/C5SC02108A] [PMID:  28717448] 
[57] 
Asensio, J.L.; Ardá, A.; Cañada, F.J.; Jiménez-Barbero, J. Carbohydrate-aromatic interactions. Acc. Chem. Res.,  2013, 46(4), 946-954.
[http://dx.doi.org/10.1021/ar300024d] [PMID:  22704792] 
[58] 
Somovilla, V.J.; Bermejo, I.A.; Albuquerque, I.S.; Martínez-Sáez, N.; Castro-López, J.; García-Martín, F.; Compañón, I.; Hinou, H.; Nishimura, S-I.; Jiménez-Barbero, J.; Asensio, J.L.; Avenoza, A.; Busto, J.H.; Hurtado-Guerrero, R.; Peregrina, J.M.; Bernardes, G.J.L.; Corzana, F. The use of fluoroproline in MUC1 antigen enables efficient detection of antibodies in patients with prostate cancer. J. Am. Chem. Soc.,  2017, 139(50), 18255-18261.
[http://dx.doi.org/10.1021/jacs.7b09447] [PMID:  29166012] 
[59] 
Dokurno, P.; Bates, P.A.; Band, H.A.; Stewart, L.M.D.; Lally, J.M.; Burchell, J.M.; Taylor-Papadimitriou, J.; Snary, D.; Sternberg, M.J.E.; Freemont, P.S. Crystal structure at 1.95 A resolution of the breast tumour-specific antibody SM3 complexed with its peptide epitope reveals novel hypervariable loop recognition. J. Mol. Biol.,  1998, 284(3), 713-728.
[http://dx.doi.org/10.1006/jmbi.1998.2209] [PMID:  9826510] 
[60] 
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(5), 1132-1135.
[http://dx.doi.org/10.1016/j.bmc.2016.01.044] [PMID:  26853835] 
[61] 
Bermejo, I.A.; Navo, C.D.; Castro-López, J.; Guerreiro, A.; Jiménez-Moreno, E.; Sánchez Fernández, E.M.; García-Martín, F.; Hinou, H.; Nishimura, S-I.; García Fernández, J.M.; Mellet, C.O.; Avenoza, A.; Busto, J.H.; Bernardes, G.J.L.; Hurtado-Guerrero, R.; Peregrina, J.M.; Corzana, F. Synthesis, conformational analysis and in vivo assays of an anti-cancer vaccine that features an unnatural antigen based on an sp2-iminosugar fragment. Chem. Sci.,  2020, 11(15), 3996-4006.
[http://dx.doi.org/10.1039/C9SC06334J] [PMID:  34122869] 
[62] 
Sánchez-Fernández, E.M.; Rísquez-Cuadro, R.; Ortiz Mellet, C.; García Fernández, J.M.; Nieto, P.M.; Angulo, J. sp2-Iminosugar O-, S-, and N-glycosides as conformational mimics of α-linked disaccharides; implications for glycosidase inhibition. Chem. Eur. J.,  2012, 18(27), 8527-8539.
[http://dx.doi.org/10.1002/chem.201200279] [PMID:  22674827] 
[63] 
Fernández, E.M.; Navo, C.D.; Martínez-Sáez, N.; Gonçalves-Pereira, R.; Somovilla, V.J.; Avenoza, A.; Busto, J.H.; Bernardes, G.J.L.; Jiménez-Osés, G.; Corzana, F.; Fernández, J.M.; Mellet, C.O.; Peregrina, J.M. Tn antigen mimics based on sp(2)-iminosugars with affinity for an anti-MUC1 antibody. Org. Lett.,  2016, 18(15), 3890-3893.
[http://dx.doi.org/10.1021/acs.orglett.6b01899] [PMID:  27453399] 
[64] 
Zhu, J.; Wan, Q.; Lee, D.; Yang, G., 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(26), 9298-9303.
[http://dx.doi.org/10.1021/ja901415s] [PMID:  19518111] 
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DOI https://dx.doi.org/10.2174/0929867328666210810152917	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Structure-based Design of Anti-cancer Vaccines: The Significance of Antigen Presentation to Boost the Immune Response

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