title: Whole-Cell Cancer Vaccines Induce Large Antibody Responses to Carbohydrates and Glycoproteins.
abstract: 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.
authors.affiliation: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 376 Boyles Street, Room 208, Frederick, MD 21702, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xia
authors.affiliation: Thoracic Oncology Section, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Schrump
authors.affiliation: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 376 Boyles Street, Room 208, Frederick, MD 21702, USA. Electronic address: gildersj@mail.nih.gov.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Gildersleeve
keywords: anti-glycan antibody; carbohydrate antigen; glycan microarray; immunotherapy; whole-cell vaccine