Qendro Veneta, Lundgren Deborah H, Palczewski Samuel, Hegde Poornima, Stevenson Christina, Perpetua Laurie, Latifi Ardian, Merriman Jesse, Bugos Grace, Han David K
Center for Vascular Biology, Department of Cell Biology, University of Connecticut School of Medicine, Farmington, CT, USA.
Department of Anatomic Pathology and Laboratory Medicine, University Connecticut Health Center, Farmington, CT, USA.
Proteomics. 2017 Aug;17(15-16). doi: 10.1002/pmic.201600318.
Recent advances in cancer immuno-therapeutics such as checkpoint inhibitors, chimeric antigen-receptor T cells, and tumor infiltrating T cells (TIL) are now significantly impacting cancer patients in a positive manner. Although very promising, reports indicate no more than 25% of cases result in complete remission. One of the limitations of these treatments is the identity of putative cancer antigens in each patient, as it is technically challenging to identify cancer antigens in a rapid fashion. Thus, identification of cancer antigens followed by targeted treatment will increase the efficacy of cancer immunotherapies. To achieve this goal, a combined technologies platform of deep genomic sequencing and personalized immune assessment was devised, termed Genomics Driven Immunoproteomics (GDI). Using this technological platform, we report the discovery of 149 tumor antigens from human breast cancer patients. Significant number of these putative cancer antigens arise from single nucleotide variants (SNVs), as well as insertions and deletions that results into frame-shift mutations. We propose a general model of anti-cancer immunity and suggest that the GDI platform may help identify patient-specific tumor antigens in a timely fashion for precision immunotherapies.
癌症免疫疗法的最新进展，如检查点抑制剂、嵌合抗原受体T细胞和肿瘤浸润T细胞（TIL），目前正以积极的方式显著影响着癌症患者。尽管前景非常广阔，但报告显示，只有不超过25%的病例能实现完全缓解。这些治疗方法的局限性之一在于每个患者体内假定癌症抗原的特性，因为快速鉴定癌症抗原在技术上具有挑战性。因此，鉴定癌症抗原并进行靶向治疗将提高癌症免疫疗法的疗效。为实现这一目标，设计了一个将深度基因组测序和个性化免疫评估相结合的技术平台，称为基因组驱动免疫蛋白质组学（GDI）。利用这个技术平台，我们报告了从人类乳腺癌患者中发现了149种肿瘤抗原。这些假定的癌症抗原中有相当一部分来自单核苷酸变异（SNV）以及导致移码突变的插入和缺失。我们提出了一种抗癌免疫的通用模型，并表明GDI平台可能有助于及时鉴定患者特异性肿瘤抗原，以进行精准免疫治疗。
