Xia Li, Schrump David S, Gildersleeve Jeffrey C
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 376 Boyles Street, Room 208, Frederick, MD 21702, USA.
Thoracic Oncology Section, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Chem Biol. 2016 Dec 22;23(12):1515-1525. doi: 10.1016/j.chembiol.2016.10.012. Epub 2016 Nov 23.
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.
全细胞癌症疫苗是一种很有前景的癌症治疗策略，但对良好免疫反应的特征尚未完全了解。新的见解有助于开发更好的疫苗、发现新的抗原并确定疗效生物标志物。我们使用糖抗原微阵列证明，GVAX胰腺疫苗（一种粒细胞巨噬细胞集落刺激因子修饰的全细胞肿瘤疫苗）可诱导针对许多抗原产生大量免疫球蛋白G和免疫球蛋白M反应，这些抗原包括肿瘤相关碳水化合物、血型抗原、α-Gal和牛胎球蛋白。对α-Gal（一种存在于用于生产疫苗的胎牛血清中的聚糖）的抗体反应与总生存期呈负相关，并且似乎与对疫苗的有效反应相互竞争。用胎牛血清生产的H1299裂解物疫苗也诱导了对α-Gal和胎球蛋白的反应，但在无血清培养基中生产的K562-GM疫苗则未诱导此类反应。我们的结果提供了新的潜在生物标志物，以评估有效/无效的免疫反应，并表明去除/减少胎牛血清可提高全细胞疫苗的疗效。
