Effect of yeast-derived beta-glucan in conjunction with bevacizumab for the treatment of human lung adenocarcinoma in subcutaneous and orthotopic xenograft models.
Human lung cancer is the leading cause of cancer death worldwide. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), in combination with chemotherapy showed significant therapeutic efficacy in human lung cancer patients. However, increased adverse effects limit its clinical utilization. Previous studies demonstrated that polysaccharide beta-glucan significantly augments antitumor monoclonal antibody-mediated efficacy via stimulation of the innate effector neutrophil complement receptor 3. Here, we explored combined beta-glucan with bevacizumab therapy for human lung cancer using murine xenograft models. To that end, human lung adenocarcinomas were screened for membrane-bound VEGF expression. Both subcutaneous and orthotopic lung cancer xenograft models were used to evaluate the combination therapy. We found that PC14PE6 adenocarcinoma cells express membrane-bound VEGF both in vitro and in vivo. Bevacizumab bound to surface VEGF on PC14PE6 cells and activated complement. In the subcutaneous PC14PE6 tumor model, beta-glucan plus bevacizumab showed augmented efficacy in terms of tumor progression and long-term survival compared with bevacizumab-treated alone. These effects were accompanied with massive complement deposition and neutrophil infiltration within tumors. However, this effect was not observed in surface-bound VEGF-negative human lung tumors. Therapeutic efficacy of beta-glucan with bevacizumab was further demonstrated in an orthotopic lung cancer model. Thus, our data suggest that beta-glucan enhances bevacizumab-mediated efficacy and may provide therapeutic benefits for lung cancers with membrane-bound VEGF expression.
Zhong
Wangjian
W
Tumor Immunobiology Program of the James Graham Brown Cancer Center, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Hansen
Richard
R
Li
Bing
B
Cai
Yihua
Y
Salvador
Carolina
C
Moore
Grace D
GD
Yan
Jun
J
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D020556:Neutrophil Infiltration / Q000276:immunology; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D015003:Yeasts / Q000737:chemistry; D047071:beta-Glucans / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D047071:beta-Glucans; D000068258:Bevacizumab