Whole-Cell Cancer Vaccines Induce Large Antibody Responses to Carbohydrates and Glycoproteins. Issue 12 (22nd December 2016)

• Record Type: Journal Article
• Authors: Xia, Li; Schrump, David S.; Gildersleeve, Jeffrey C.
• Is Part Of: Cell chemical biology. Volume 23:Issue 12(2016)
• Page Start: 1515
• Page End: 1525
• Publication Date: 2016-12-22
• Subjects: whole-cell vaccine -- glycan microarray -- anti-glycan antibody -- carbohydrate antigen -- immunotherapy; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2016.10.012
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: Whole-cell cancer vaccines are a promising strategy for treating cancer, but the characteristics of a favorable immune response are not fully understood. New insights could enable development of better vaccines, discovery of new antigens, and identification of biomarkers of efficacy. Using glyco-antigen microarrays, we demonstrate that GVAX Pancreas (a granulocyte macrophage colony-stimulating factor-modified whole-cell tumor vaccine) induces large immunoglobulin G and immunoglobulin M responses to many antigens, including tumor-associated carbohydrates, blood group antigens, α-Gal, and bovine fetuin. Antibody responses to α-Gal, a glycan found in fetal bovine serum (FBS) used to produce the vaccine, correlated inversely with overall survival and appear to compete with productive responses to the vaccine. H1299 lysate vaccine, produced with FBS, also induced responses to α-Gal and fetuin but not K562-GM, which is produced in serum-free medium. Our results provide new potential biomarkers to evaluate productive/unproductive immune responses and suggest that removal/reduction of FBS could improve the efficacy of whole-cell vaccines. Graphical Abstract: Highlights: Antibody responses to a whole-cell vaccine were profiled with a glycan microarray Large IgG and IgM responses to FBS antigens and tumor antigens were observed Responses to non-human antigens correlated inversely with patient survival Responses to non-human antigens out-compete productive response to the vaccine Abstract : Glycan microarrays were used to profile anti-carbohydrate antibody responses induced by whole-cell vaccines. Large IgG and IgM responses were detected, and certain responses correlated with survival. The results provide new indicators of vaccine efficacy and provide simple strategies to improve whole-cell vaccines.