{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:07:21Z","timestamp":1790806041424,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFC3400800"],"award-info":[{"award-number":["2022YFC3400800"]}]},{"name":"National Key Research and Development Program of China","award":["22177003"],"award-info":[{"award-number":["22177003"]}]},{"name":"National Key Research and Development Program of China","award":["22237001"],"award-info":[{"award-number":["22237001"]}]},{"name":"National Key Research and Development Program of China","award":["2021QRECM01"],"award-info":[{"award-number":["2021QRECM01"]}]},{"name":"National Natural Science Foundation of China","award":["2022YFC3400800"],"award-info":[{"award-number":["2022YFC3400800"]}]},{"name":"National Natural Science Foundation of China","award":["22177003"],"award-info":[{"award-number":["22177003"]}]},{"name":"National Natural Science Foundation of China","award":["22237001"],"award-info":[{"award-number":["22237001"]}]},{"name":"National Natural Science Foundation of China","award":["2021QRECM01"],"award-info":[{"award-number":["2021QRECM01"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["2022YFC3400800"],"award-info":[{"award-number":["2022YFC3400800"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["22177003"],"award-info":[{"award-number":["22177003"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["22237001"],"award-info":[{"award-number":["22237001"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["2021QRECM01"],"award-info":[{"award-number":["2021QRECM01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>KH-1 is a tumor-associated carbohydrate antigen (TACA), which serves as a valuable target of antitumor vaccines for cancer immunotherapies. However, most TACAs are thymus-independent antigens (TD-Ag), and they tend to induce immunological tolerance, leading to their low immunogenicity. To overcome these problems, some fluorinated derivatives of the KH-1 antigen were designed, synthesized, and conjugated to the carrier protein CRM197 to form glycoconjugates, which were used for immunological studies with Freund\u2019s adjuvant. The results showed that fluorine-modified N-acyl KH-1 conjugates can induce higher titers of antibodies, especially IgG, which can recognize KH-1-positive cancer cells and can eliminate cancer cells through complement-dependent cytotoxicity (CDC). The trifluoro-modified KH-1-TF-CRM197 showed great potential as an anticancer vaccine candidate.<\/jats:p>","DOI":"10.3390\/molecules28041934","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T02:02:09Z","timestamp":1676858529000},"page":"1934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cancer Vaccines Based on Fluorine-Modified KH-1 Elicit Robust Immune Response"],"prefix":"10.3390","volume":"28","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. No. 38, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. No. 38, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujing","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. No. 38, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5187-9313","authenticated-orcid":false,"given":"Decai","family":"Xiong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. No. 38, Beijing 100191, China"},{"name":"The NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-Based Medicine, Shandong University, 27 Shanda Nanlu, Jinan 250100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinshan","family":"Ye","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. No. 38, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nrc3982","article-title":"Glycosylation in cancer: Mechanisms and clinical implications","volume":"15","author":"Pinho","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1136\/mp.52.4.174","article-title":"Lewis blood group and CEA related antigens; coexpressed cell-cell adhesion molecules with roles in the biological progression and dissemination of tumors","volume":"52","author":"Sanders","year":"1999","journal-title":"Mol. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1089\/mab.2021.0024","article-title":"Tumor-associated glycans as targets for immunotherapy: The Wistar institute experience\/legacy","volume":"40","author":"Thurin","year":"2021","journal-title":"Monoclon. Antib. Immunodiagn. Immunother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8802","DOI":"10.1016\/j.vaccine.2011.09.009","article-title":"Cancer vaccines and carbohydrate epitopes","volume":"29","author":"Lum","year":"2011","journal-title":"Vaccine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/978-1-4615-1267-7_24","article-title":"Tumor-associated carbohydrate antigens defining tumor malignancy: Basis for development of anti-cancer vaccines","volume":"491","author":"Hakomori","year":"2001","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/1044-579X(95)90005-5","article-title":"Augmenting the immunogenicity of carbohydrate tumor antigens","volume":"6","author":"Livingston","year":"1995","journal-title":"Semin. Cancer Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1158\/1078-0432.CCR-03-0101","article-title":"Vaccination of small cell lung cancer patients with polysialic acid or N-propionylated polysialic acid conjugated to keyhole limpet hemocyanin","volume":"10","author":"Krug","year":"2004","journal-title":"Clin Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/bs.accb.2017.10.003","article-title":"The synthesis and biological characterization of acetal-free mimics of the tumor-associated carbohydrate antigens","volume":"74","author":"Sadraei","year":"2017","journal-title":"Adv. Carbohydr. Chem. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1021\/bk-2008-0990.ch010","article-title":"Synthesis and evaluation of anticancer vaccine candidates: C-glycoside analogues of STn and PSA","volume":"990","author":"Weiwer","year":"2008","journal-title":"ACS Symp. Ser."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7725","DOI":"10.1002\/anie.200502179","article-title":"Thiooligosaccharide conjugate vaccines evoke antibodies specific for native antigens","volume":"44","author":"Bundle","year":"2005","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8498","DOI":"10.1002\/anie.201003810","article-title":"Synthetic antitumor vaccines from tetanus toxoid conjugates of MUC1 glycopeptides with the Thomsen-Friedenreich antigen and a fluorine-substituted analogue","volume":"49","author":"Kaiser","year":"2010","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11247","DOI":"10.1016\/S0021-9258(18)67375-2","article-title":"Novel fucolipids of human adenocarcinoma: Characterization of the major Ley antigen of human adenocarcinoma as trifucosylnonaosyl Ley glycolipid (III3FucV3FucVI2FucnLc6)","volume":"261","author":"Nudelman","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11254","DOI":"10.1016\/S0021-9258(18)67376-4","article-title":"Novel fucolipids of human adenocarcinoma: Monoclonal antibody specific for trifucosyl Ley (III3FucV3FucVI2FucnLc6) and a possible three-dimensional epitope structure","volume":"261","author":"Kaizu","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_14","first-page":"2183","article-title":"Highly tumor-reactive, internalizing, mouse monoclonal antibodies to Le(y)-related cell surface antigens","volume":"50","author":"Garrigues","year":"1990","journal-title":"Cancer Res."},{"key":"ref_15","first-page":"5985","article-title":"Expression of Ley and extended Ley blood group-related antigens in human malignant, premalignant, and nonmalignant colonic tissues","volume":"46","author":"Kim","year":"1986","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1042\/bj2680275","article-title":"Expression of the CD15 differentiation antigen (3-fucosyl-N-acetyl-lactosamine, LeX) on putative neutrophil adhesion molecules CR3 and NCA-160","volume":"268","author":"Stocks","year":"1990","journal-title":"Biochem. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5457","DOI":"10.1002\/chem.200500412","article-title":"Synthesis of a dimeric Lewis antigen and the evaluation of the epitope specificity of antibodies elicited in mice","volume":"11","author":"Buskas","year":"2005","journal-title":"Chem. Eur. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/387164a0","article-title":"Total synthesis of the potential anticancer vaccine KH-1 adenocarcinoma antigen","volume":"387","author":"Deshpande","year":"1997","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1021\/jo048016l","article-title":"Synthesis of selected LeY and KH-1 analogues:\u2009 A medicinal chemistry approach to vaccine optimization","volume":"70","author":"Spassova","year":"2005","journal-title":"J. Org. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/S0040-4039(97)00006-3","article-title":"A versatile synthesis of the lactoneo-series antigens\u2014Synthesis of sialyl dimer Lewis X and of dimer Lewis Y","volume":"38","author":"Hummel","year":"1997","journal-title":"Tetrahedron Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/ange.200352539","article-title":"Automated solid-phase synthesis of protected tumor-associated antigen and blood group determinant oligosaccharides","volume":"116","author":"Seeberger","year":"2004","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6558","DOI":"10.1021\/acs.orglett.7b03275","article-title":"Synthesis of the cancer-associated KH-1 antigen by block assembly of its backbone structure followed by one-step grafting of three fucose residues","volume":"19","author":"Li","year":"2017","journal-title":"Org. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1021\/cb100287q","article-title":"Enhancement of the immunogenicity of synthetic carbohydrate vaccines by chemical modifications of STn antigen","volume":"6","author":"Yang","year":"2011","journal-title":"ACS Chem. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1039\/D1MD00067E","article-title":"Synthesis and immunological evaluation of N-acyl modified Globo H derivatives as anticancer vaccine candidates","volume":"12","author":"Zhai","year":"2021","journal-title":"RSC Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s10719-019-09884-0","article-title":"Fluorine-modified sialyl-Tn-CRM197 vaccine elicits a robust immune response","volume":"36","author":"Song","year":"2019","journal-title":"Glycoconj. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"47330","DOI":"10.18632\/oncotarget.17646","article-title":"A cancer vaccine based on fluorine-modified sialyl-Tn induces robust immune responses in a murine model","volume":"8","author":"Song","year":"2017","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1039\/D0QO00314J","article-title":"Total synthesis of tumor-associated KH-1 antigen core nonasaccharide via photo-induced glycosylation","volume":"7","author":"Li","year":"2020","journal-title":"Org. Chem. Front."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5221","DOI":"10.1002\/anie.200460176","article-title":"Iterative one-pot synthesis of oligosaccharides","volume":"43","author":"Huang","year":"2004","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5606","DOI":"10.1021\/acs.orglett.5b02823","article-title":"Photoinduced C-S bond cleavage of thioglycosides and glycosylation","volume":"17","author":"Mao","year":"2015","journal-title":"Org. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1039\/C6QO00021E","article-title":"Light-driven highly efficient glycosylation reactions","volume":"3","author":"Mao","year":"2016","journal-title":"Org. Chem. Front."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1586\/14760584.2016.1115726","article-title":"Update on the use of meningococcal serogroup C CRM197-conjugate vaccine (Meningitec) against meningitis","volume":"15","author":"Badahdah","year":"2016","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1073\/pnas.1222649110","article-title":"Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer","volume":"110","author":"Huang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0968-4328(99)00036-0","article-title":"Keyhole limpet hemocyanin (KLH): A biomedical review","volume":"30","author":"Harris","year":"1999","journal-title":"Micron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/pola.20463","article-title":"Synthesis and characterization of novel biodegradable unsaturated poly(ester amide)s","volume":"43","author":"Guo","year":"2005","journal-title":"J. Polym. Sci. A Polym. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5903","DOI":"10.1073\/pnas.0710799105","article-title":"Rational chemical design of the carbohydrate in a glycoconjugate vaccine enhances IgM-to-IgG switching","volume":"105","author":"Guttormsen","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/med.21493","article-title":"Carbohydrate-based vaccines for oncotherapy","volume":"38","author":"Wei","year":"2018","journal-title":"Med. Res. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev.iy.08.040190.001511","article-title":"Lymphokine control of in vivo immunoglobulin isotype selection","volume":"8","author":"Finkelman","year":"1990","journal-title":"Annu. Rev. Immunol."},{"key":"ref_38","first-page":"1553","article-title":"Expression of Lewis a, Lewis b, X, and Y blood group antigens in human colonic tumors and normal tissue and in human tumor-derived cell lines","volume":"46","author":"Sakamoto","year":"1986","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107999","DOI":"10.1016\/j.carres.2020.107999","article-title":"Comparative immunological studies of tumor-associated Lewis X, Lewis Y, and KH-1 antigens","volume":"492","author":"Guo","year":"2020","journal-title":"Carbohydr. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s12016-019-08741-0","article-title":"Complement system: A neglected pathway in immunotherapy","volume":"58","author":"Bordron","year":"2020","journal-title":"Clin. Rev. Allergy. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.molimm.2014.06.010","article-title":"How antibodies use complement to regulate antibody responses","volume":"61","author":"Zhang","year":"2014","journal-title":"Mol. Immunol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1934\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:39:59Z","timestamp":1760121599000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,17]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28041934"],"URL":"https:\/\/doi.org\/10.3390\/molecules28041934","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,17]]}}}