ABSTRACT

Chemorefractory ovarian cancer has limited therapeutic options. Hence, new types of treatment including neoantigen-specific immunotherapy need to be investigated. Neoantigens represent promising targets for personalized cancer immunotherapy. We here describe the clinical and immunological effects of a neoantigen peptide-loaded DC-based immunotherapy in a patient with recurrent and chemoresistant ovarian cancer. A 71-year-old female patient with chemorefractory ovarian cancer and malignant ascites received intranodal vaccination of DCs loaded with four neoantigen peptides that were predicted by our immunogenomic pipeline. Following four rounds of vaccinations with this therapy, CA-125 levels were remarkably declined and tumor cells in the ascites were also decreased. Concordantly, the tumor-related symptoms such as respiratory discomfort improved without any adverse reactions. The reactivity against one HLA-A2402-restricted neoantigen peptide derived from a mutated PPM1 F protein was detected in lymphocytes from peripheral blood by IFN-γ ELISPOT assay. Furthermore, the neoantigen (PPM1 F mutant)-specific TCRs were detected in the tumor-infiltrating T lymphocytes post-vaccination. Our results showed that vaccination with intranodal injection of neoantigen peptide-loaded DCs may have clinical and immunological impacts on cancer treatment.

摘要

化学难治性卵巢癌的治疗选择有限。因此，需要研究包括新抗原特异性免疫疗法在内的新型治疗方法。新抗原代表了个性化癌症免疫治疗的有希望的目标。我们在此描述了基于新抗原肽的 DC 免疫疗法对复发性和耐药性卵巢癌患者的临床和免疫学效果。一名患有化学难治性卵巢癌和恶性腹水的 71 岁女性患者接受了负载有四种新抗原肽的 DC 的结内疫苗接种，这些肽是我们的免疫基因组学管道预测的。在用这种疗法接种四轮疫苗后，CA-125 水平显着下降，腹水中的肿瘤细胞也减少了。一致地，肿瘤相关症状如呼吸不适等改善，无任何不良反应。通过 IFN-γ ELISPOT 测定法在外周血淋巴细胞中检测到对一种源自突变 PPM1 F 蛋白的 HLA-A2402 限制性新抗原肽的反应性。此外，在接种疫苗后的肿瘤浸润 T 淋巴细胞中检测到新抗原（PPM1 F 突变体）特异性 TCR。我们的结果表明，结内注射新抗原肽负载 DCs 的疫苗接种可能对癌症治疗产生临床和免疫学影响。在接种疫苗后的肿瘤浸润 T 淋巴细胞中检测到新抗原（PPM1 F 突变体）特异性 TCR。我们的结果表明，结内注射新抗原肽负载 DCs 的疫苗接种可能对癌症治疗产生临床和免疫学影响。在接种疫苗后的肿瘤浸润 T 淋巴细胞中检测到新抗原（PPM1 F 突变体）特异性 TCR。我们的结果表明，结内注射新抗原肽负载 DCs 的疫苗接种可能对癌症治疗产生临床和免疫学影响。