PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
树突状细胞(DC)疫苗在肿瘤免疫治疗中的疗效常因抗原交叉呈递(XPT)效率低下导致的免疫原性较弱而受到限制。
英文原题:A Personalized Neoantigen Vaccine in Combination with Platinum-Based Chemotherapy Induces a T-Cell Response Coinciding with a Complete Response in Endometrial Carcinoma.
子宫内膜癌(EC)是一种常见的妇科恶性肿瘤,也是欧洲和北美女性中第四常见的恶性肿瘤。
子宫内膜癌(EC)是常见的妇科恶性肿瘤,也是欧洲和北美女性中第四常见的恶性肿瘤。在EC中,晚期浆液性、p53突变型和pMMR亚型尽管接受了最佳标准治疗,复发风险仍最高。目前,对于这些高危患者,尚无标准的一线维持治疗来预防复发。疫苗是一种免疫治疗形式,可能增强pMMR、浆液性和p53突变型肿瘤的免疫原性,使其对基于检查点抑制剂的免疫治疗产生应答。我们首次证明,在一位pMMR、p53突变型浆液性子宫内膜腺癌(SEC)患者中,制备负载肽新抗原的个体化树突状细胞疫苗是可行的。该个体化疫苗与全身化疗联合用于治疗无法手术的转移性复发。这种治疗联合证明了个体化树突状细胞疫苗的安全性和免疫原性。有趣的是,在影像学评估和肿瘤标志物CA-125方面均获得了完全的肿瘤学缓解。
Endometrial cancer (EC) is a common gynecological malignancy and the fourth most common malignancy in European and North American women. Amongst EC, the advanced serous, p53-mutated, and pMMR subtypes have the highest risk of relapse despite optimal standard of care therapy. At present, there is no standard of care maintenance treatment to prevent relapse among these high-risk patients. Vaccines are a form of immunotherapy that can potentially increase the immunogenicity of pMMR, serous, and p53-mutated tumors to render them responsive to check point inhibitor-based immunotherapy. We demonstrate, for the first time, the feasibility of generating a personalized dendritic cell vaccine pulsed with peptide neoantigens in a patient with pMMR, p53-mutated, and serous endometrial adenocarcinoma (SEC). The personalized vaccine was administered in combination with systemic chemotherapy to treat an inoperable metastatic recurrence. This treatment association demonstrated the safety and immunogenicity of the personalized dendritic cell vaccine. Interestingly, a complete oncological response was obtained with respect to both radiological assessment and the tumor marker CA-125.
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