IN-VITRO AND IN-VIVO HEMATOPOIETIC ACTIVITIES OF BETAFECTIN(R) PGG-GLUCAN

Betafectin(R) PGG-glucan is a novel beta-(1,3)glucan that has broad-sp ectrum anti-infective activities without cytokine induction. Here we r eport that PGG-glucan also has both in vitro and in vivo hematopoietic activities. In vitro studies with bone marrow target cells from the C 3H/HeN mouse revealed that although PGG-glucan alone had no direct eff ect on hematopoietic colony-forming cell (CFC) growth, when combined w ith granulocyte colony-stimulating factor (CSF) or granulocyte-macroph age CSF, it increased CFC numbers 1.5- to 2.0-fold over those obtained with CSFs alone. Bone marrow cells cultured for high-proliferative-po tential CFCs in the presence of interleukin (IL)-1, IL-3, macrophage C SF, and stem cell factor (SCF), or cultured for erythroid burst-formin g units in the presence of IL-3, SCF, and erythropoietin, also exhibit ed enhanced growth in the presence of PGG-glucan. The synergistic effe ct of PGG-glucan was specific and could be abrogated by anti-PGG-gluca n antibody. The ability of PGG-glucan to modulate hematopoiesis in viv o was evaluated in myelosuppressed rodents and primates. C3H/HeN femal e mice were intravenously administered saline solution or PGG-glucan ( 0.5 mg/kg) 24 hours before the intraperitoneal administration of cyclo phosphamide (200 mg/kg), and the recovery of bone marrow cellularity a nd granulocyte-macrophage progenitor cells was evaluated on days 4 and 8 after cyclophosphamide treatment. At both time points, enhanced hem atopoietic recovery was observed in PGG-glucan-treated mice compared w ith saline-treated control mice. In a final series of in vivo experime nts, we evaluated the ability of therapeutically administered PGG-gluc an to enhance hematopoietic recovery in cyclophosphamide-treated cynom olgus monkeys. Monkeys received intravenous infusions of cyclophospham ide (55 mg/kg) on days 1 and 2, followed on days 3 and 10 by intraveno us infusion of PGG-glucan (0.5, 1.0, or 2.0 mg/kg). Compared with thos e in saline-treated monkeys, accelerated white blood cell recovery and a reduction in the median duration of neutropenia were observed in PG G-glucan-treated monkeys. These studies illustrate that PGG-glucan has both in vitro and in vivo hematopoietic activities and that this agen t may be useful in the prevention and/or treatment of chemotherapy-ass ociated myelosuppression.