Oral (1-->3),(1-->4)-beta-D-glucan synergizes with antiganglioside GD2 monoclonal antibody 3F8 in the therapy of neuroblastoma.

Abstract

PURPOSE:

In vitro beta-glucan can enhance tumor cytotoxicity through iC3b receptors on leukocytes. We tested if (1-->3),(1-->4)-beta-D-glucan (beta-glucan) can synergize with anti-GD2 monoclonal antibody (MoAb) 3F8 (mouse IgG3) in therapy of human neuroblastoma xenografts.

EXPERIMENTAL DESIGN:

Athymic nude mice with established neuroblastoma xenografts were treated with daily i.p. or p.o. beta-glucan, in the presence/absence of i.v. MoAb twice a week, for 22-29 days. Serial tumor volumes and body weights were monitored.

RESULTS:

3F8 plus beta-glucan produced near-complete tumor regression/disease stabilization, whereas 3F8 or beta-glucan alone did not significantly affect tumor growth. For NMB7 tumors, median survival of 3F8 plus beta-glucan group was 5.5-fold that of control groups (P < 0.001), and for LAN-1, the survival difference was 2.6-fold. Forty-seven percent of the mice with NMB7 and 18% with LAN-1 remained progression free in contrast to <3% of controls. Antitumor effect was seen at > or =40 microg of glucan dose, i.v. or p.o., and in all human neuroblastoma cell lines tested. No toxicities were noted in mice treated with either beta-glucan alone or 3F8 plus beta-glucan (4-4000 microg/dose). In contrast to anti-GD2 MoAb 3G6 (IgM), 3F8 F(ab')(2) and MoAb 8H9 (IgG1) did not activate complement and had no synergy with beta-glucan. Antitumor effect of 3F8 plus p.o. beta-glucan persisted after antiasialo-GM1 antibody treatment, as well as in NK-deficient host.

CONCLUSIONS:

p.o. 1,3-1,4-beta-glucan synergized with antitumor IgG and IgM MoAb in vivo. Because beta-glucan was well tolerated and inexpensive, its potential value in cancer therapy deserves further investigation.

• Authors: Nai-Kong V Cheung, Shakeel Modak
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 8 Issue 5 Pg. 1217-23 (May 2002) ISSN: 1078-0432 [Print] United States
• PMID: 12006541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Gangliosides
• Glucans
• beta-Glucans
• beta-glucan, (1-3)(1-4)-

Topics

• Administration, Oral
• Animals
• Antibodies, Monoclonal (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Synergism
• Gangliosides (immunology)
• Glucans (administration & dosage, pharmacology)
• Humans
• Injections, Intraperitoneal
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mice, SCID
• Neoplasm Transplantation
• Neuroblastoma (drug therapy, mortality, pathology)
• Survival Analysis
• Survival Rate
• Time Factors
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• beta-Glucans