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Chemoenzymatic Synthesis of 9NHAc-GD2 Antigen to Overcome the Hydrolytic Instability of O-Acetylated-GD2 for Anticancer Conjugate Vaccine Development

  1. Author:
    Wu, Xuanjun
    Ye, Jinfeng
    DeLaitsch, Andrew T.
    Rashidijahanabad, Zahra
    Lang, Shuyao
    Kakeshpour, Tayeb
    Zhao, Yuetao
    Ramadan, Sherif
    Saavedra, Paulo Vilar
    Yuzbasiyan-Gurkan, Vilma
    Kavunja, Herbert
    Cao, Hongzhi
    Gildersleeve,Jeffrey
    Huang, Xuefei

  2. Author Address

    Shandong Univ, Shandong Key Lab Carbohydrate Chem & Glycobiol, Natl Glycoengn Res Ctr, Qingdao 266237, Shandong, Peoples R China.Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA.Michigan State Univ, Inst Quantitat Hlth Sci & Engn, E Lansing, MI 48824 USA.NCI, Chem Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.Cent South Univ, Sch Life Sci, Changsha 410013, Hunan, Peoples R China.Benha Univ, Fac Sci, Chem Dept, Banha 13518, Qaliobiya, Egypt.Michigan State Univ, Dept Small Anim Clin Sci, E Lansing, MI 48824 USA.Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.Iaso Therapeut, 4942 Dawn Ave, E Lansing, MI 48823 USA.Michigan State Univ, Dept Biomed Engn, E Lansing, MI 48824 USA.
    1. Year: 2021
    2. Date: Nov 2
    3. Epub Date: 2021 09 01
  2. Journal: Angewandte Chemie (International ed. in English)
  3. WILEY-V C H VERLAG GMBH,
    1. 60
    2. 45
    3. Pages: 24179-24188
  5. Type of Article: Article
  6. ISSN: 1433-7851
  1. Abstract:

    Ganglioside GD2 is an attractive tumor-associated carbohydrate antigen for anti-cancer vaccine development. However, its low immunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines. To overcome these, a new GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), a GD2 based antigen with a restricted expression on tumor cells. 9NHAc-GD2 was synthesized efficiently via a chemoenzymatic method and subsequently conjugated with a powerful carrier bacteriophage Q beta. Mouse immunization with the Q beta-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward 9NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Q beta-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects, paving the way for future clinical translation to humans.

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External Sources

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  2. DOI: 10.1002/anie.202108610
  3. PMID: 34469031
  4. PMCID: PMC8545922
  5. View record in Web of Science®
  6. WOS: 000703115800001

Library Notes

  1. Fiscal Year: FY2021-2022
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