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

Oral (1-->3),(1-->4)-beta-D-glucan synergizes with antiganglioside GD2 monoclonal antibody 3F8 in the therapy of neuroblastoma.
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发表时间:
2002-05
期刊:
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子:
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通讯作者:
N. Cheung;S. Modak
N. Cheung;S. Modak
中科院分区:
其他
文献类型:
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作者:
N. Cheung;S. Modak

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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 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.