Mechanism by which orally administered β-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models Journal Article
| Authors: | Hong, F.; Yan, J.; Baran, J. T.; Allendorf, D. J.; Hansen, R. D.; Ostroff, G. R.; Xing, P. X.; Cheung, N. K. V.; Ross, G. D. |
| Article Title: | Mechanism by which orally administered β-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models |
| 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 autitumor 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. |
| Keywords: | controlled study; treatment failure; human cell; nonhuman; neoplasms; animal cell; mouse; animals; mice; animal tissue; cell survival; bone marrow; spleen; animal experiment; animal model; antineoplastic activity; cytotoxicity; tumor regression; tumor cell culture; monoclonal antibody; antibodies, monoclonal; drug mechanism; cd11b antigen; lymph node; tumor cell line; immunological adjuvant; mucin 1; adjuvants, immunologic; macrophage; macrophages; lymphoid tissue; beta 1,3 glucan; lewis carcinoma; granulocyte; beta-glucans; beta 1,6 glucan; complement component c3b receptor; glucans; barley; opsonization; cd18 antigen; complement c3; complement activation; human; priority journal; article; macrophage-1 antigen |
| Journal Title: | Journal of Immunology |
| Volume: | 173 |
| Issue: | 2 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2004-07-15 |
| Start Page: | 797 |
| End Page: | 806 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 15240666 |
| DOI: | 10.4049/jimmunol.173.2.797 |
| DOI/URL: | |
| Notes: | J. Immunol. -- Cited By (since 1996):205 -- Export Date: 16 June 2014 -- CODEN: JOIMA C2 - 15240666 -- Source: Scopus |
