Purpose: Glioblastoma (GBM) patient outcomes remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax. Patients and Methods: Here, we report the findings of four subjects enrolled onto the NeoVax clinical trial (NCT0342209). Results: Immune reactivity to NeoVax neoantigens was assessed in peripheral blood mononuclear cells (PBMCs) pre- and post-NeoVax for subjects 1-3 using IFNg-ELISPOT assay. A statistically significant increase in IFNg producing T cells at the post-NeoVax time point for several neoantigens was observed. Furthermore, a post-NeoVax tumor biopsy was obtained from subject 3 and, upon evaluation, revealed evidence of infiltrating, clonally expanded T cells. Conclusions: Collectively, our findings suggest NeoVax did stimulate expansion of neoantigen-specific effector T cells and provide encouraging results to aid in the development of future neoantigen vaccine-based clinical trials in patients with GBM. Herein, we demonstrate the feasibility of incorporating multisector sampling in cancer vaccine design and provide information on the clinical applicability of clonality, distribution, and immunogenicity of the neoantigen landscape in GBM patients.

中文翻译：

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将多部门分子特征整合到新诊断的胶质母细胞瘤患者的个性化肽疫苗设计中

目的：尽管采用手术、放疗和化疗等多模式治疗，胶质母细胞瘤 (GBM) 患者的预后仍然较差。由于缺乏肿瘤免疫原性，免疫治疗选择很少。一些临床试验报告了癌症疫苗的有希望的结果。迄今为止，研究已使用来自单个肿瘤部位的数据来识别可靶向抗原，但这种方法限制了抗原库，并且与 GBM 的异质性相反。我们已经实施了多部门测序，以增加 GBM 基因组景观中的新抗原库，这些新抗原可以纳入名为 NeoVax 的个性化肽疫苗中。患者和方法：在这里，我们报告了参加 NeoVax 临床试验 (NCT0342209) 的四名受试者的结果。结果：使用 IFNg-ELISPOT 测定评估了受试者 1-3 在 NeoVax 治疗前和治疗后的外周血单核细胞 (PBMC) 中对 NeoVax 新抗原的免疫反应性。在 NeoVax 后的时间点，观察到几种新抗原产生 IFNg 的 T 细胞出现统计学上显着的增加。此外，对受试者 3 进行了 NeoVax 后肿瘤活检，经过评估，发现了浸润性、克隆性扩增的 T 细胞的证据。结论：总的来说，我们的研究结果表明 NeoVax 确实刺激了新抗原特异性效应 T 细胞的扩增，并提供了令人鼓舞的结果，以帮助未来在 GBM 患者中开展基于新抗原疫苗的临床试验。在此，我们证明了在癌症疫苗设计中纳入多部门采样的可行性，并提供了 GBM 患者新抗原景观的克隆性、分布和免疫原性的临床适用性信息。