The Biodesign Institute Center for Innovations in Medicine, Arizona State University, Tempe, AZ, USA.
Stanford University, Stanford, CA, USA.
Sci Rep. 2019 Oct 2;9(1):14184. doi: 10.1038/s41598-019-50738-4.
The success of checkpoint inhibitors in cancer therapy is largely attributed to activating the patient's immune response to their tumor's neoantigens arising from DNA mutations. This realization has motivated the interest in personal cancer vaccines based on sequencing the patient's tumor DNA to discover neoantigens. Here we propose an additional, unrecognized source of tumor neoantigens. We show that errors in transcription of microsatellites (MS) and mis-splicing of exons create highly immunogenic frameshift (FS) neoantigens in tumors. The sequence of these FS neoantigens are predictable, allowing creation of a peptide array representing all possible neoantigen FS peptides. This array can be used to detect the antibody response in a patient to the FS peptides. A survey of 5 types of cancers reveals peptides that are personally reactive for each patient. This source of neoantigens and the method to discover them may be useful in developing cancer vaccines.
检查点抑制剂在癌症治疗中的成功在很大程度上归因于激活患者对其肿瘤源自 DNA 突变的新抗原的免疫反应。这一认识激发了人们对基于对患者肿瘤 DNA 进行测序以发现新抗原的个性化癌症疫苗的兴趣。在这里，我们提出了肿瘤新抗原的另一个未被认识的来源。我们表明，微卫星 (MS) 的转录错误和外显子的错误剪接会在肿瘤中产生高度免疫原性的移码 (FS) 新抗原。这些 FS 新抗原的序列是可预测的，允许创建一个代表所有可能的新抗原 FS 肽的肽阵列。该阵列可用于检测患者对 FS 肽的抗体反应。对 5 种癌症的调查揭示了针对每个患者的个人反应肽。这种新抗原的来源和发现它们的方法可能对开发癌症疫苗有用。
