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Mechanism by Which Orally Administered β-1,3-Glucans Enhance the Tumoricidal Activity of Antitumor Monoclonal Antibodies in Murine Tumor Models

2004; American Association of Immunologists; Volume: 173; Issue: 2 Linguagem: Inglês

10.4049/jimmunol.173.2.797

1550-6606

Hong Feng, Jun Yan, Jarosław Baran, Daniel J. Allendorf, Richard Hansen, Gary R. Ostroff, Pei Xiang Xing, Nai‐Kong V. Cheung, Gordon D. Ross,

Wnt/β-catenin signaling in development and cancer

Abstract Antitumor mAb bind to tumors and activate complement, coating tumors with iC3b. Intravenously administered yeast β-1,3;1,6-glucan functions as an adjuvant for antitumor mAb by priming the inactivated C3b (iC3b) receptors (CR3; CD11b/CD18) of circulating granulocytes, enabling CR3 to trigger cytotoxicity of iC3b-coated tumors. Recent data indicated that barley β-1,3;1,4-glucan given orally similarly potentiated the activity of antitumor mAb, leading to enhanced tumor regression and survival. This investigation showed that orally administered yeast β-1,3;1,6-glucan functioned similarly to barley β-1,3;1,4-glucan with antitumor mAb. With both oral β-1,3-glucans, a requirement for iC3b on tumors and CR3 on granulocytes was confirmed by demonstrating therapeutic failures in mice deficient in C3 or CR3. Barley and yeast β-1,3-glucan were labeled with fluorescein to track their oral uptake and processing in vivo. Orally administered β-1,3-glucans were taken up by macrophages that transported them to spleen, lymph nodes, and bone marrow. Within the bone marrow, the macrophages degraded the large β-1,3-glucans into smaller soluble β-1,3-glucan fragments that were taken up by the CR3 of marginated granulocytes. These granulocytes with CR3-bound β-1,3-glucan-fluorescein were shown to kill iC3b-opsonized tumor cells following their recruitment to a site of complement activation resembling a tumor coated with mAb.