Tanyi Janos L, Chiang Cheryl L-L, Chiffelle Johanna, Thierry Anne-Christine, Baumgartener Petra, Huber Florian, Goepfert Christine, Tarussio David, Tissot Stephanie, Torigian Drew A, Nisenbaum Harvey L, Stevenson Brian J, Guiren Hajer Fritah, Ahmed Ritaparna, Huguenin-Bergenat Anne-Laure, Zsiros Emese, Bassani-Sternberg Michal, Mick Rosemarie, Powell Daniel J, Coukos George, Harari Alexandre, Kandalaft Lana E
Ovarian Cancer Research Center, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Oncology, Lausanne University Hospital (CHUV), Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.
NPJ Vaccines. 2021 Mar 15;6(1):36. doi: 10.1038/s41541-021-00297-5.
T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specific T cells and prolonged OC survival. Here, we hypothesize that adding acetylsalicylic acid (ASA) and low-dose interleukin (IL)-2 would increase the vaccine efficacy in a recurrent advanced OC phase I trial (NCT01132014). By adding ASA and low-dose IL-2 to the OCDC-Bev-Cy combinatorial regimen, we elicited vaccine-specific T-cell responses that positively correlated with patients' prolonged time-to-progression and overall survival. In the ID8 ovarian model, animals receiving the same regimen showed prolonged survival, increased tumor-infiltrating perforin-producing T cells, increased neoantigen-specific CD8 T cells, and reduced endothelial Fas ligand expression and tumor-infiltrating T-regulatory cells. This combinatorial strategy was efficacious and also highlighted the predictive value of the ID8 model for future ovarian trial development.
T细胞对于控制卵巢癌（OC）至关重要。我们之前证明，个性化全肿瘤裂解物脉冲树突状细胞疫苗（OCDC）、贝伐单抗（Bev）和环磷酰胺（Cy）联合使用可引发新抗原特异性T细胞并延长OC患者的生存期。在此，我们假设在一项复发性晚期OC I期试验（NCT01132014）中添加乙酰水杨酸（ASA）和低剂量白细胞介素（IL）-2会提高疫苗疗效。通过在OCDC-Bev-Cy联合方案中添加ASA和低剂量IL-2，我们引发了与患者延长的疾病进展时间和总生存期呈正相关的疫苗特异性T细胞反应。在ID8卵巢模型中，接受相同方案的动物生存期延长，肿瘤浸润性产生穿孔素的T细胞增加，新抗原特异性CD8 T细胞增加，内皮细胞Fas配体表达降低，肿瘤浸润性调节性T细胞减少。这种联合策略是有效的，也突出了ID8模型对未来卵巢试验开发的预测价值。
