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


METHODS
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.
Cheung
Nai-Kong V
NK
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. cheungn@mskcc.org
Modak
Shakeel
S
D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005732:Gangliosides / Q000276:immunology*; D005936:Glucans / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D047071:beta-Glucans
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D005936:Glucans; D047071:beta-Glucans; C067858:beta-glucan, (1-3)(1-4)-