Orally administered β-glucans enhance anti-tumor effects of monoclonal antibodies Journal Article

Authors: Cheung, N. K. V.; Modak, S.; Vickers, A.; Knuckles, B.
Article Title: Orally administered β-glucans enhance anti-tumor effects of monoclonal antibodies
Abstract: β-Glucan primes leukocyte CR3 for enhanced cytotoxicity and synergizes with anti-tumor monoclonal antibodies (mAb). We studied readily available (1→3)-β-D-glucan using the immune deficient xenograft tumor models, and examined the relationship of its anti-tumor effect and physico-chemical properties. Established subcutaneous (s.c.) human xenografts were treated for 29 days orally with daily β-glucan by intragastric injection and mAb intravenously (i.v.) twice weekly. Control mice received either mAb alone or β-glucan alone. Tumor sizes were monitored over time. β-Glucans were studied by carbohydrate linkage analysis, and high performance size-exclusion chromatography with multiple angle laser scattering detection. Orally administered β-D-glucan greatly enhanced the anti-tumor effects of mAb against established tumors in mice. We observed this β-glucan effect irrespective of antigen (GD2, GD3, CD20, epidermal growth factor-receptor, HER-2), human tumor type (neuroblastoma, melanoma, lymphoma, epidermoid carcinoma and breast carcinoma) or tumor sites (s.c. versus systemic). This effect correlated with the molecular size of the (1→3),(1→4)-β-D-glucan. Orally administered (1→3),(1→6)-β-D-glucans also synergized with mAb, although the effect was generally less marked. Given the favorable efficacy and toxicity profile of oral β-D-glucan treatment, the role of natural products that contain β-glucan in cancer treatment as an enhancer of the effect of mAb therapy deserves further study.
Keywords: controlled study; unclassified drug; oncoprotein; human cell; squamous cell carcinoma; drug efficacy; drug potentiation; nonhuman; antineoplastic agents; combined modality therapy; rituximab; mouse; animals; mice; cell division; tumor localization; melanoma; tumor volume; epidermal growth factor receptor; epidermal growth factor receptor 2; analytic method; animal experiment; animal model; antineoplastic activity; cytotoxicity; drug effect; drug screening; tumor cells, cultured; xenograft model antitumor assays; monoclonal antibody; drug synergism; cd20 antigen; antibodies, monoclonal; immunotherapy; kinetics; xenograft; mice, nude; neuroblastoma; ganglioside gd2; breast carcinoma; lymphoma; neoplasms, experimental; tumor immunity; high performance liquid chromatography; trastuzumab; beta glucan; administration, oral; molecular weight; beta 1,3 glucan; ganglioside gd3; physical chemistry; monoclonal antibody 3f8; beta-glucans; linkage analysis; beta 1,6 glucan; monoclonal antibody 8h9; glucans; humans; human; priority journal; article; monoclonal antibody r24; beta 1,4 glucan; monoclonal antibody 3g6; (1→3),(1→4)-β-d-glucan; adcc; cmc; cr3
Journal Title: Cancer Immunology, Immunotherapy
Volume: 51
Issue: 10
ISSN: 0340-7004
Publisher: Springer  
Date Published: 2002-11-01
Start Page: 557
End Page: 564
Language: English
PUBMED: 12384807
PROVIDER: scopus
DOI: 10.1007/s00262-002-0321-3
Notes: Export Date: 14 November 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Nai-Kong Cheung
    571 Cheung
  2. Shakeel Modak
    201 Modak
  3. Andrew J Vickers
    673 Vickers