Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou, Zhejiang, China.
Clin Cancer Res. 2020 Sep 1;26(17):4511-4520. doi: 10.1158/1078-0432.CCR-19-2881. Epub 2020 May 21.
Because of their high tumor specificity and immunogenicity, neoantigens have been considered as ultimate targets for cancer immunotherapy. Neoantigen-based vaccines have demonstrated promising efficacy for several cancer types. To further investigate the antitumor potentials for other types of solid tumors, we designed a peptide-based neoantigen vaccine, iNeo-Vac-P01, and conducted a single-arm, open-labeled, investigator-initiated clinical trial (NCT03662815).
Personalized neoantigen vaccines were designed and manufactured according to our bioinformatics analysis results from the whole-exome sequencing of tumor and peripheral blood cell DNAs. Patients were scheduled to be vaccinated subcutaneously with adjuvant on days 1, 4, 8, 15, and 22 (prime phase), and days 78 and 162 (boost phase). Additional immunizations were administrated every 2-3 months as per patient's potential benefit. The safety and efficacy were assessed through adverse events (AE), progression-free survival (PFS), overall survival (OS), and other parameters.
Of the 22 patients enrolled with advanced malignancies, 20 had no or mild AEs, while 2 had grade 3 or 4 acute allergic reactions only after their sixth boost vaccination. The disease control rate was 71.4%. The median PFS was 4.6 months, whereas the median OS was not reached (12-month OS = 55.1%). Around 80% of individual peptides or peptide pools elicited measurable specific immune response. In addition, our findings revealed several potential biomarkers for the prediction of better response.
iNeo-Vac-P01 as monotherapy is feasible and safe for patients with advanced solid tumors. It could elicit T-cell-mediated immune response targeting tumor neoantigens, and might have promising antitumor efficacy..
由于其高肿瘤特异性和免疫原性，新抗原被认为是癌症免疫治疗的终极靶点。基于新抗原的疫苗已在多种癌症类型中显示出良好的疗效。为了进一步研究其对其他类型实体瘤的抗肿瘤潜力，我们设计了一种基于肽的新抗原疫苗 iNeo-Vac-P01，并进行了一项单臂、开放标签、研究者发起的临床试验（NCT03662815）。
根据我们对肿瘤和外周血 DNA 全外显子测序的生物信息学分析结果，设计并制造了个性化的新抗原疫苗。患者被安排在第 1、4、8、15 和 22 天（基础免疫）和第 78 和 162 天（加强免疫）皮下接种疫苗，并使用佐剂。根据患者的潜在获益，每 2-3 个月给予额外的免疫接种。通过不良事件（AE）、无进展生存期（PFS）、总生存期（OS）和其他参数评估安全性和疗效。
在 22 名患有晚期恶性肿瘤的患者中，20 名患者没有或仅有轻度 AE，而只有 2 名患者在第 6 次加强免疫接种后出现 3 级或 4 级急性过敏反应。疾病控制率为 71.4%。中位 PFS 为 4.6 个月，中位 OS 尚未达到（12 个月 OS = 55.1%）。约 80%的个体肽或肽池可引发可测量的特异性免疫反应。此外，我们的研究结果还发现了一些潜在的生物标志物，可用于预测更好的疗效。
iNeo-Vac-P01 作为单一疗法对晚期实体瘤患者是可行且安全的。它可以引发针对肿瘤新抗原的 T 细胞介导的免疫反应，并且可能具有有前途的抗肿瘤疗效。
