Long prime-boost interval and heightened anti-GD2 antibody response to carbohydrate cancer vaccine Journal Article


Authors: Cheung, I. Y.; Mauguen, A.; Modak, S.; Basu, E. M.; Feng, Y.; Kushner, B. H.; Cheung, N. K.
Article Title: Long prime-boost interval and heightened anti-GD2 antibody response to carbohydrate cancer vaccine
Abstract: The carbohydrate ganglioside GD2/GD3 cancer vaccine adjuvanted by beta-glucan stimulates anti-GD2 IgG1 antibodies that strongly correlate with improved progression-free survival (PFS) and overall survival (OS) among patients with high-risk neuroblastoma. Thirty-two patients who relapsed on the vaccine (first enrollment) were re-treated on the same vaccine protocol (re-enrollment). Titers during the first enrollment peaked by week 32 at 751 +/- 270 ng/mL, which plateaued despite vaccine boosts at 1.2-4.5 month intervals. After a median wash-out interval of 16.1 months from the last vaccine dose during the first enrollment to the first vaccine dose during re-enrollment, the anti-GD2 IgG1 antibody rose to a peak of 4066 +/- 813 ng/mL by week 3 following re-enrollment (p < 0.0001 by the Wilcoxon matched-pairs signed-rank test). Yet, these peaks dropped sharply and continually despite repeated boosts at 1.2-4.5 month intervals, before leveling off by week 20 to the first enrollment peak levels. Despite higher antibody titers, patients experienced no pain or neuropathic side effects, which were typically associated with immunotherapy using monoclonal anti-GD2 antibodies. By the Kaplan-Meier method, PFS was estimated to be 51%, and OS was 81%. The association between IgG1 titer during re-enrollment and beta-glucan receptor dectin-1 SNP rs3901533 was significant (p = 0.01). A longer prime-boost interval could significantly improve antibody responses in patients treated with ganglioside conjugate cancer vaccines.
Keywords: immunogenicity; beta-glucan; diphtheria; trial; monoclonal-antibodies; melanoma patients; high-risk neuroblastoma; ganglioside; gd2; hemocyanin conjugate vaccine; crm197; ganglioside gd2/gd3 carbohydrate vaccine; anti-gd2 igg1 titer; dectin-1 snp rs3901533; pertussis-vaccine
Journal Title: Vaccines
Volume: 12
Issue: 6
ISSN: 2076-393X
Publisher: MDPI  
Date Published: 2024-06-01
Start Page: 587
Language: English
ACCESSION: WOS:001257145000001
DOI: 10.3390/vaccines12060587
PROVIDER: wos
PMCID: PMC11209353
PUBMED: 38932316
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Irene Y. Cheung -- Source: Wos
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MSK Authors
  1. Brian Kushner
    311 Kushner
  2. Nai-Kong Cheung
    648 Cheung
  3. Shakeel Modak
    249 Modak
  4. Irene Y Cheung
    96 Cheung
  5. Yongqiang Feng
    9 Feng
  6. Ellen Marlese Basu
    101 Basu
  7. Yi Feng
    15 Feng
  8. Audrey   Mauguen
    155 Mauguen