Orally administered beta-glucans enhance anti-tumor effects of monoclonal antibodies.
beta-Glucan primes leukocyte CR3 for enhanced cytotoxicity and synergizes with anti-tumor monoclonal antibodies (mAb). We studied readily available (1-->3)-beta- 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 beta-glucan by intragastric injection and mAb intravenously (i.v.) twice weekly. Control mice received either mAb alone or beta-glucan alone. Tumor sizes were monitored over time. beta-Glucans were studied by carbohydrate linkage analysis, and high performance size-exclusion chromatography with multiple angle laser scattering detection. Orally administered beta- D-glucan greatly enhanced the anti-tumor effects of mAb against established tumors in mice. We observed this beta-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)-beta- D-glucan. Orally administered (1-->3),(1-->6)-beta- D-glucans also synergized with mAb, although the effect was generally less marked. Given the favorable efficacy and toxicity profile of oral beta- D-glucan treatment, the role of natural products that contain beta-glucan in cancer treatment as an enhancer of the effect of mAb therapy deserves further study.
Cheung
Nai-Kong V
NK
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. cheungn@mskcc.org
Modak
Shakeel
S
Vickers
Andrew
A
Knuckles
Benny
B
D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002455:Cell Division; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005936:Glucans / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D047071:beta-Glucans
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D005936:Glucans; D047071:beta-Glucans; C067858:beta-glucan, (1-3)(1-4)-; C033363:beta-1,3-glucan