A Vision for Vaccines Built from Fully Synthetic Tumor-associated Antigens: from the Laboratory to the Clinic

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2013 Aug 16

PMID 23944352

Citations 40

Authors

Rebecca M Wilson

Samuel J Danishefsky

Affiliations

Soon will be listed here.

Abstract

Cancer cells may be distinguished from normal cells by cell surface displays of aberrant levels and types of carbohydrate domains. Accordingly, these tumor-associated carbohydrate antigens (TACAs) represent promising target structures for the design of anticancer vaccines. Over the past 20 years, our laboratory has sought to use the tools of chemical synthesis to develop TACA-based anticancer vaccine candidates. We provide herein a personal accounting of our laboratory's progress toward the long-standing goal of developing clinically viable fully synthetic carbohydrate-based anticancer vaccines.

Citing Articles

Chemical synthesis and immunological evaluation of cancer vaccines based on ganglioside antigens and α-galactosylceramide.

Romano C, Jiang H, Tahvili S, Wei P, Keiding U, Clergeaud G RSC Med Chem. 2024; 15(8):2718-2728.

PMID: 39149099 PMC: 11324045. DOI: 10.1039/d4md00387j.

Long Prime-Boost Interval and Heightened Anti-GD2 Antibody Response to Carbohydrate Cancer Vaccine.

Cheung I, Mauguen A, Modak S, Basu E, Feng Y, Kushner B Vaccines (Basel). 2024; 12(6).

PMID: 38932316 PMC: 11209353. DOI: 10.3390/vaccines12060587.

Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses.

Bermejo I, Guerreiro A, Eguskiza A, Martinez-Saez N, Lazaris F, Asin A JACS Au. 2024; 4(1):150-163.

PMID: 38274250 PMC: 10807005. DOI: 10.1021/jacsau.3c00587.

Rapid building block-economic synthesis of long, multi--GalNAcylated MUC5AC tandem repeat peptides.

Galashov A, Kazakova E, Stieger C, Hackenberger C, Seitz O Chem Sci. 2024; 15(4):1297-1305.

PMID: 38274058 PMC: 10806717. DOI: 10.1039/d3sc05006h.

A Hitchhiker's Guide to Problem Selection in Carbohydrate Synthesis.

Streety X, Obike J, Townsend S ACS Cent Sci. 2023; 9(7):1285-1296.

PMID: 37521800 PMC: 10375882. DOI: 10.1021/acscentsci.3c00507.

References

Zhang S, Zhang H, Reuter V, Slovin S, Scher H, Livingston P . Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers. Clin Cancer Res. 1998; 4(2):295-302. View

De Silva R, Wang Q, Chidley T, Appulage D, Andreana P . Immunological response from an entirely carbohydrate antigen: design of synthetic vaccines based on Tn-PS A1 conjugates. J Am Chem Soc. 2009; 131(28):9622-3. DOI: 10.1021/ja902607a. View

Kaiser A, Gaidzik N, Westerlind U, Kowalczyk D, Hobel A, Schmitt E . 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(41):7551-5. DOI: 10.1002/anie.200902564. View

Gaidzik N, Westerlind U, Kunz H . The development of synthetic antitumour vaccines from mucin glycopeptide antigens. Chem Soc Rev. 2013; 42(10):4421-42. DOI: 10.1039/c3cs35470a. View

Hoffmann-Roder A, Kaiser A, Wagner S, Gaidzik N, Kowalczyk D, Westerlind U . 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):8498-503. DOI: 10.1002/anie.201003810. View

Zhang S, Cordon-Cardo C, Zhang H, Reuter V, Adluri S, Hamilton W . Selection of tumor antigens as targets for immune attack using immunohistochemistry: I. Focus on gangliosides. Int J Cancer. 1997; 73(1):42-9. DOI: 10.1002/(sici)1097-0215(19970926)73:1<42::aid-ijc8>3.0.co;2-1. View

Yin Z, Huang X . Recent Development in Carbohydrate Based Anti-cancer Vaccines. J Carbohydr Chem. 2012; 31(3):143-186. PMC: 3312792. DOI: 10.1080/07328303.2012.659364. View

Yin Z, Nguyen H, Chowdhury S, Bentley P, Bruckman M, Miermont A . Tobacco mosaic virus as a new carrier for tumor associated carbohydrate antigens. Bioconjug Chem. 2012; 23(8):1694-703. PMC: 3426870. DOI: 10.1021/bc300244a. View

Buskas T, Ingale S, Boons G . 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. 2005; 44(37):5985-8. DOI: 10.1002/anie.200501818. View

10.

Ingale S, Wolfert M, Gaekwad J, Buskas T, Boons G . Robust immune responses elicited by a fully synthetic three-component vaccine. Nat Chem Biol. 2007; 3(10):663-7. PMC: 2836923. DOI: 10.1038/nchembio.2007.25. View

11.

Ragupathi G, Koide F, Livingston P, Cho Y, Endo A, Wan Q . 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(8):2715-25. DOI: 10.1021/ja057244+. View

12.

Ragupathi G, Coltart D, Williams L, Koide F, Kagan E, Allen J . On the power of chemical synthesis: immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines. Proc Natl Acad Sci U S A. 2002; 99(21):13699-704. PMC: 129747. DOI: 10.1073/pnas.202427599. View

13.

Ragupathi G, Koide F, Sathyan N, Kagan E, Spassova M, Bornmann W . A preclinical study comparing approaches for augmenting the immunogenicity of a heptavalent KLH-conjugate vaccine against epithelial cancers. Cancer Immunol Immunother. 2003; 52(10):608-16. PMC: 11041859. DOI: 10.1007/s00262-003-0399-2. View

14.

Zhu J, Wan Q, Lee D, Yang G, Spassova M, Ouerfelli O . From synthesis to biologics: preclinical data on a chemistry derived anticancer vaccine. J Am Chem Soc. 2009; 131(26):9298-303. PMC: 2716484. DOI: 10.1021/ja901415s. View

15.

Zhu , Boons . A Two-Directional and Highly Convergent Approach for the Synthesis of the Tumor-Associated Antigen Globo-H. Angew Chem Int Ed Engl. 1999; 38(23):3495-3497. DOI: 10.1002/(sici)1521-3773(19991203)38:23<3495::aid-anie3495>3.0.co;2-x. View

16.

Wilson R, Danishefsky S . On the reach of chemical synthesis: creation of a mini-pipeline from an academic laboratory. Angew Chem Int Ed Engl. 2010; 49(35):6032-56. DOI: 10.1002/anie.201000775. View

17.

Wang Z, Zhou L, El-Boubbou K, Ye X, Huang X . Multi-component one-pot synthesis of the tumor-associated carbohydrate antigen Globo-H based on preactivation of thioglycosyl donors. J Org Chem. 2007; 72(17):6409-20. PMC: 2533580. DOI: 10.1021/jo070585g. View

18.

Zhu J, Warren J, Danishefsky S . Synthetic carbohydrate-based anticancer vaccines: the Memorial Sloan-Kettering experience. Expert Rev Vaccines. 2009; 8(10):1399-413. PMC: 3063993. DOI: 10.1586/erv.09.95. View

19.

Zhang S, Zhang H, Cordon-Cardo C, Reuter V, Singhal A, LLOYD K . Selection of tumor antigens as targets for immune attack using immunohistochemistry: II. Blood group-related antigens. Int J Cancer. 1997; 73(1):50-6. DOI: 10.1002/(sici)1097-0215(19970926)73:1<50::aid-ijc9>3.0.co;2-0. View

20.

Yin Z, Comellas-Aragones M, Chowdhury S, Bentley P, Kaczanowska K, BenMohamed L . Boosting immunity to small tumor-associated carbohydrates with bacteriophage qβ capsids. ACS Chem Biol. 2013; 8(6):1253-62. PMC: 3735802. DOI: 10.1021/cb400060x. View