Oral (1→3),(1→4)-β-D-glucan synergizes with antiganglioside GD2 monoclonal antibody 3F8 in the therapy of neuroblastoma Journal Article

Authors: Cheung, N. K. V.; Modak, S.
Article Title: Oral (1→3),(1→4)-β-D-glucan synergizes with antiganglioside GD2 monoclonal antibody 3F8 in the therapy of neuroblastoma
Abstract: Purpose: In vitro β-glucan can enhance tumor cytotoxicity through iC3b receptors on leukocytes. We tested if (1→3),(1→4)-β-D-glucan (β-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. β-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 β-glucan produced near-complete tumor regression/disease stabilization, whereas 3F8 or β-glucan alone did not significantly affect tumor growth. For NMB7 tumors, median survival of 3F8 plus β-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 ≥40 μg 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 β-glucan alone or 3F8 plus β-glucan (4-4000 μg/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 β-glucan. Antitumor effect of 3F8 plus p.o. β-glucan persisted after antiasialo-GM1 antibody treatment, as well as in NK-deficient host. Conclusions: p.o. 1,3-1,4-β-glucan synergized with antitumor IgG and IgM MoAb in vivo. Because β-glucan was well tolerated and inexpensive, its potential value in cancer therapy deserves further investigation.
Keywords: survival; cancer survival; controlled study; survival analysis; survival rate; unclassified drug; human cell; drug tolerability; mortality; dose response; drug potentiation; nonhuman; mouse; animal; mouse mutant; animals; mice; tumor volume; drug administration schedule; animal experiment; animal model; body weight; antineoplastic activity; cytotoxicity; tumor regression; drug screening; pathology; dose-response relationship, drug; mice, scid; tumor cells, cultured; xenograft model antitumor assays; mice, inbred balb c; time; time factors; monoclonal antibody; drug synergism; immunology; antibodies, monoclonal; bagg albino mouse; cell culture; nude mouse; mice, nude; neuroblastoma; ganglioside gd2; natural killer cell; ganglioside gm1; neoplasm transplantation; drug administration; beta glucan; administration, oral; beta 1,3 glucan; monoclonal antibody 3f8; beta-glucans; oral drug administration; cancer transplantation; gangliosides; ganglioside; ganglioside antibody; intraperitoneal drug administration; injections, intraperitoneal; monoclonal antibody 8h9; glucans; complement activation; glucan; humans; human; priority journal; article; beta 1,4 glucan; monoclonal antibody 3g6; beta glucan, (1 3)(1 4); beta-glucan, (1-3)(1-4)-
Journal Title: Clinical Cancer Research
Volume: 8
Issue: 5
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2002-05-01
Start Page: 1217
End Page: 1223
Language: English
PUBMED: 12006541
PROVIDER: scopus
Notes: Export Date: 14 November 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Nai-Kong Cheung
    571 Cheung
  2. Shakeel Modak
    201 Modak