Oral (133),(134)- -D-Glucan Synergizes with Antiganglioside GD2 Monoclonal Antibody 3F8 in the Therapy of Neuroblastoma

Purpose: In vitro -glucan can enhance tumor cytotoxicity through iC3b receptors on leukocytes. We tested if (133),(134)-D-glucan ( -glucan) can synergize with antiGD2 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. -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 -glucan produced near-complete tumor regression/disease stabilization, whereas 3F8 or glucan alone did not significantly affect tumor growth. For NMB7 tumors, median survival of 3F8 plus -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 g 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 -glucan alone or 3F8 plus -glucan (4–4000 g/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 -glucan. Antitumor effect of 3F8 plus p.o. -glucan persisted after antiasialo-GM1 antibody treatment, as well as in