Therapeutic potential of various beta-glucan sources in conjunction with anti-tumor monoclonal antibody in cancer therapy.
Combined beta-glucan with anti-tumor mAb therapy has demonstrated therapeutic efficacy in murine tumor models. The current study was designed to compare the therapeutic efficacy of various sources of beta-glucans. Our studies demonstrated that yeast beta-glucan, in combination with anti-tumor mAb, resulted in significantly smaller tumor burdens and achieved enhanced long-term survival compared to mAb alone or beta-glucan extracts from mushrooms. Further studies indicated that yeast beta-glucan particle was superior to mushroom extracts in inducing cytokine secretion, particularly IL-12 production in dendritic cells (DCs). In addition, results showed that cytokine production was markedly decreased in MyD88-deficient macrophages and DCs but not in complement receptor 3 (CR3)-deficient mice. Our data suggest that yeast beta-glucan demonstrates much stronger adjuvant activity compared to mushroom beta-glucan extracts in tumor therapy. This effect of yeast beta-glucan may be in part ascribed to the cytokine secretion by DCs and macrophages and bioavailability of active beta-glucan moiety.
Driscoll
Michael
M
Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202 , USA.
Hansen
Richard
R
Ding
Chuanlin
C
Cramer
Daniel E
DE
Yan
Jun
J
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000954:Antigens, Surface / Q000032:analysis / Q000096:biosynthesis; D018929:Cell Culture Techniques; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019587:Dietary Supplements; D048691:Grifola / Q000737:chemistry; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D020940:Reishi / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D020942:Shiitake Mushrooms / Q000737:chemistry; D016896:Treatment Outcome; D047071:beta-Glucans / Q000008:administration & dosage* / Q000737:chemistry
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; C434325:MUC-1 monoclonal antibody; D047071:beta-Glucans; D018664:Interleukin-12