Phase I trial of oral yeast-derived β-glucan to enhance anti-GD2 immunotherapy of resistant high-risk neuroblastoma Journal Article
| Authors: | Iglesias Cardenas, F.; Mauguen, A.; Cheung, I. Y.; Kramer, K.; Kushner, B. H.; Ragupathi, G.; Cheung, N. K. V.; Modak, S. |
| Article Title: | Phase I trial of oral yeast-derived β-glucan to enhance anti-GD2 immunotherapy of resistant high-risk neuroblastoma |
| Abstract: | Beta glucans, complex polysaccharides, prime leukocyte dectin-1 and CR3-receptors and enhance anti-tumor cytotoxicity of complement-activating monoclonal antibodies. We conducted a phase I study (clinicaltrials.gov NCT00492167) to determine the safety of the combination of yeast-derived beta glucan (BG) and anti-GD2 murine monoclonal antibody 3F8 in patients with relapsed or refractory high-risk neuroblastoma. Patients received intravenous 3F8 (fixed dose of 10 mg/m2 /day × 10 days) and oral BG (dose-escalated from 10–200 mg/kg/day × 17 days in cohorts of 3–6 patients each). Forty-four patients completed 141 cycles. One patient developed DLT: transient self-limiting hepatic transaminase elevation 5 days after starting BG (120 mg/kg/day). Overall, 1, 3, 12 and 24 evaluable patients had complete response, partial response, stable and progressive disease, respectively, at the end of treatment. Positive human anti-mouse antibody response and dectin-1 rs3901533 polymorphism were associated with better overall survival. BG dose level and serum BG levels did not correlate with response. Progression-free and overall survival at 2 years were 28% and 61%, respectively. BG lacked major toxicity. Treatment with 3F8 plus BG was associated with anti-neuroblastoma responses in patients with resistant disease. Although the maximal tolerated dose for yeast BG was not reached, considering the large volume of oral BG, we recommended 40 mg/kg/day as the phase II dose. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
| Keywords: | neuroblastoma; β-glucan; anti-gd2 antibody |
| Journal Title: | Cancers |
| Volume: | 13 |
| Issue: | 24 |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Date Published: | 2021-12-14 |
| Start Page: | 6265 |
| Language: | English |
| DOI: | 10.3390/cancers13246265 |
| PROVIDER: | scopus |
| PMCID: | PMC8699451 |
| PUBMED: | 34944886 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 January 2022 -- Source: Scopus |
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