Ovarian Cancer Research Center, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Oncology, Lausanne University Hospital, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne CH-1066, Switzerland.
Sci Transl Med. 2018 Apr 11;10(436). doi: 10.1126/scitranslmed.aao5931.
We conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1, = 5), in combination with bevacizumab (cohort 2, = 10), or bevacizumab plus low-dose intravenous cyclophosphamide (cohort 3, = 10) until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events. Vaccination induced T cell responses to autologous tumor antigen, which were associated with significantly prolonged survival. Vaccination also amplified T cell responses against mutated neoepitopes derived from nonsynonymous somatic tumor mutations, and this included priming of T cells against previously unrecognized neoepitopes, as well as novel T cell clones of markedly higher avidity against previously recognized neoepitopes. We conclude that the use of oxidized whole-tumor lysate DC vaccine is safe and effective in eliciting a broad antitumor immunity, including private neoantigens, and warrants further clinical testing.
我们进行了一项试点临床试验,测试了一种由自体树突状细胞(DC)脉冲氧化自体全肿瘤细胞裂解物(OCDC)制成的个体化疫苗,将其皮内注射到铂类治疗、免疫治疗初治、复发性卵巢癌患者中。OCDC 单独给药(队列 1,n=5),联合贝伐珠单抗(队列 2,n=10)或贝伐珠单抗联合低剂量静脉环磷酰胺(队列 3,n=10),直到疾病进展或疫苗耗尽。共给予 392 剂疫苗,无严重不良事件。疫苗接种诱导了针对自体肿瘤抗原的 T 细胞反应,与显著延长的生存时间相关。疫苗接种还扩增了针对源自非同义体细胞突变的突变新表位的 T 细胞反应,这包括针对先前未识别的新表位的 T 细胞的启动,以及对先前识别的新表位具有明显更高亲和力的新型 T 细胞克隆。我们得出结论,使用氧化的全肿瘤裂解物 DC 疫苗在引发广泛的抗肿瘤免疫方面是安全有效的,包括个体新抗原,并值得进一步的临床测试。