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采用个体化新抗原肽疫苗对乳腺癌患者进行辅助治疗——一项回顾性观察

Adjuvant Treatment for Breast Cancer Patients Using Individualized Neoantigen Peptide Vaccination-A Retrospective Observation.

作者信息

Zelba Henning, McQueeney Alex, Rabsteyn Armin, Bartsch Oliver, Kyzirakos Christina, Kayser Simone, Harter Johannes, Latzer Pauline, Hadaschik Dirk, Battke Florian, Hartkopf Andreas D, Biskup Saskia

机构信息

Zentrum für Humangenetik Tübingen, 72076 Tuebingen, Germany.

CeGaT GmbH, 72076 Tuebingen, Germany.

出版信息

Vaccines (Basel). 2022 Nov 8;10(11):1882. doi: 10.3390/vaccines10111882.

Abstract

Breast cancer is a tumor entity that is one of the leading causes of mortality among women worldwide. Although numerous treatment options are available, current explorations of personalized vaccines have shown potential as promising new treatment options to prevent the recurrence of cancer. Here we present a small proof of concept study using a prophylactic peptide vaccination approach in four female breast cancer patients who achieved remission after standard treatment. The patients were initially analyzed for somatic tumor mutations and then treated with personalized neoantigen-derived peptide vaccines. These vaccines consisted of HLA class I and class II peptides and were administered intracutaneously followed by subcutaneous application of sargramostim and/or topical imiquimod as an immunological adjuvant. After an initial priming phase of four vaccinations within two weeks, patients received monthly boosting/maintenance vaccinations. Chemotherapy or checkpoint inhibition was not performed during vaccination. One patient received hormone therapy. The vaccines were well tolerated with no serious adverse events. All patients displayed vaccine-induced CD4+ and/or CD8+ T-cell responses against various neoantigens. Furthermore, all patients remained tumor-free and had persistent T-cell responses, even several months after the last vaccination, suggesting the potential of peptide vaccines as an immunosurveillance and long term prophylaxis option.

摘要

乳腺癌是一种肿瘤实体,是全球女性死亡的主要原因之一。尽管有多种治疗选择,但目前对个性化疫苗的探索已显示出作为预防癌症复发的有前景的新治疗选择的潜力。在此,我们展示了一项小型概念验证研究,在四名经标准治疗后实现缓解的女性乳腺癌患者中采用预防性肽疫苗接种方法。首先对患者进行体细胞肿瘤突变分析,然后用个性化的新抗原衍生肽疫苗进行治疗。这些疫苗由I类和II类 HLA 肽组成,通过皮内注射给药,随后皮下应用沙格司亭和/或局部应用咪喹莫特作为免疫佐剂。在两周内进行四次疫苗接种的初始启动阶段后,患者每月接受加强/维持疫苗接种。疫苗接种期间未进行化疗或检查点抑制。一名患者接受了激素治疗。疫苗耐受性良好,未出现严重不良事件。所有患者均表现出针对各种新抗原的疫苗诱导的CD4+和/或CD8+ T细胞反应。此外,所有患者均无肿瘤复发,并且即使在最后一次疫苗接种数月后仍有持续的T细胞反应,表明肽疫苗作为免疫监视和长期预防选择的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8317/9698403/1f2780fd5ac1/vaccines-10-01882-g001.jpg

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