Harari Alexandre, Sarivalasis Apostolos, de Jonge Kaat, Thierry Anne-Christine, Huber Florian, Boudousquie Caroline, Rossier Laetitia, Orcurto Angela, Imbimbo Martina, Baumgaertner Petra, Bassani-Sternberg Michal, Kandalaft Lana E
Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.
Ludwig Institute for Cancer Research, University of Lausanne (UNIL), 1005 Lausanne, Switzerland.
Cancers (Basel). 2021 Nov 18;13(22):5801. doi: 10.3390/cancers13225801.
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.
子宫内膜癌（EC）是一种常见的妇科恶性肿瘤，在欧洲和北美女性中是第四大常见恶性肿瘤。在子宫内膜癌中，晚期浆液性、p53突变型和错配修复缺陷（pMMR）亚型尽管接受了最佳标准治疗，但复发风险最高。目前，对于这些高危患者，尚无预防复发的标准护理维持治疗方法。疫苗是一种免疫疗法，有可能提高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疗法产生反应。我们首次证明了在一名患有pMMR、p53突变型和浆液性子宫内膜腺癌（SEC）的患者中，生成用肽新抗原脉冲的个性化树突状细胞疫苗的可行性。该个性化疫苗与全身化疗联合使用，以治疗无法手术的转移性复发。这种治疗联合证明了个性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。
