Abstract 5218: Oral beta-glucan enhanced anti-ganglioside antibody titer after vaccination against high-risk neuroblastoma: Results of a randomized trial
Authors: Cheung Irene Y. , Mauguen Audrey , Feng Yi , Ragupathi Govind , Basu Ellen , Roberts Stephen S. , Modak Shakeel , Kushner Brian H. , Cheung Nai-Kong V. 
Published: June 2022

Abstract
Background and Aim: Ganglioside GD2/GD3 vaccine stimulated robust antibody response among patients with high-risk metastatic neuroblastoma (HR-NB) who had prior disease progression (J Clin Oncol 39:215-226, 2020). High anti-GD2-IgG1antibody titer was associated with improved progression-free survival and overall survival in multivariable analyses. A gel formulation of yeast beta-glucan was used as an oral vaccine adjuvant, but its importance remained unproven.
Patients and Methods: In a follow-up randomized Phase II trial (Clinicaltrials.gov identifier: NCT00911560), seven vaccine injections at 1, 2, 3, 8, 20, 32 and 52 weeks were administered to patients with HR-NB during their first or subsequent remissions. Each subcutaneous vaccine injection consisted of 30 ug each of GD2 and GD3, which was lactonized and conjugated to keyhole limpet hemocyanin and mixed with the subcutaneous saponin OPT-821 adjuvant at 150 µg/m2. No patients in this analysis received prior ganglioside vaccine. They were randomized to Arm 1 (n=54) receiving no glucan, or Arm 2 (n=53) receiving oral beta-glucan regimen (40 mg/kg/day, 14 days on/14 days off) starting at week 1. From week 6 onwards, all 107 patients received oral beta-glucan regimen through year end or up to disease progression. Serum IgG1 against GD2 and GD3, and IgM against GD2 were measured by ELISA at (right before) each vaccine injection. Wilcoxon rank sum test was used to compare antibody titers between the 2 arms.
Results: In both arms, patients had comparable disease status at study entry, with 70% each in first remission. The remaining patients were in second remission after one prior disease progression. Consistently higher antibody response was observed among Arm 2 patients. The primary endpoint was met for anti-GD2-IgG1 titer at vaccine injection #6 at 32 weeks (p=0.08). Per protocol design, statistical significance (p&lt;0.1) of anti-GD2-IgG1titer was observed at vaccine #5 (2.7-fold), #6 (1.4-fold), and #7 (4.1-fold), irrespective of being in first or second remission at study entry. Total anti-GD2-IgG1 antibody exposure (AUC) up to vaccine #7 for Arm 2 was 1.9-fold higher than that of Arm 1 (p=0.05). In contrast, anti-GD2-IgM achieved statistical significance only at vaccine #4 (p=0.001), and for anti-GD3-IgG1, only at vaccine #5 (p=0.07). Oral beta-glucan was well tolerated, and no patient showed pain or neuropathic side effects despite having higher antibody titers.
Conclusion: Adding oral yeast beta-glucan as vaccine adjuvant during the first 6 weeks of immunization significantly enhanced the anti-GD2-IgG1 antibody response without added toxicities. Its impact on patient survival will require a longer clinical follow-up.
Citation Format: Irene Y. Cheung, Audrey Mauguen, Yi Feng, Govind Ragupathi, Ellen Basu, Stephen S. Roberts, Shakeel Modak, Brian H. Kushner, Nai-Kong V. Cheung. Oral beta-glucan enhanced anti-ganglioside antibody titer after vaccination against high-risk neuroblastoma: Results of a randomized trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5218.