合成长肽和DNA个体化癌症疫苗在胰腺癌中诱导强烈的新抗原特异性T细胞应答
Synthetic long peptide and DNA personalized cancer vaccines induce robust neoantigen-specific T cell responses in pancreatic cancer
胰腺导管腺癌（PDAC）对现有免疫治疗基本无反应。研究者开展了两项1期临床试验，为手术切除并完成辅助化疗的患者接种合成长肽或DNA个体化癌症疫苗（根据患者肿瘤测序结果定制的疫苗），疫苗耐受良好，未出现3级及以上不良事件。检测发现疫苗诱导出新抗原特异性T细胞应答，且这些T细胞受体被确认能识别新抗原。与同期倾向性匹配的院内队列相比，接种疫苗者中位总生存期呈延长趋势（4.4年对3.5年），但差异无统计学意义。
为什么推荐给您：个体化新抗原疫苗在难治胰腺癌的早期人体阳性免疫应答，属新模态重要进展
不需要生物学背景，多打比方
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摘要Abstract
Pancreatic ductal adenocarcinoma (PDAC) is unresponsive to standard immunotherapies despite harboring cancer neoantigens capable of eliciting T cell responses. We completed two phase 1 clinical trials (NCT03956056 and NCT03122106) evaluating safety and immunogenicity of synthetic long peptide (SLP) and DNA personalized cancer vaccines (PCVs). PCVs were administered after resection and adjuvant chemotherapy. Tumor/normal whole-exome sequencing, RNA sequencing, and pVACtools were used to identify and prioritize candidate PCV neoantigens. PCVs were well tolerated without any grade ≥3 adverse events. Neoantigen-specific responses were demonstrated by interferon-γ enzyme-linked immunospot and intracellular cytokine staining. Expanded T cell receptor clonotypes were sequenced and transduced into autologous peripheral blood mononuclear cells to confirm neoantigen specificity. When compared with a contemporaneous institutional propensity-matched cohort, PCV patients demonstrated a trend toward prolonged median overall survival (4.4 versus 3.5 years, log-rank P = 0.23). Overall, PDAC PCVs are safe and feasible and elicit polyclonal T cell responses, linking prioritized cancer neoantigens to functional antitumor immunity.