Department of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Immunotherapy. 2019 Aug;11(11):953-966. doi: 10.2217/imt-2019-0055. Epub 2019 Jun 13.
The purpose of this study was to determine whether addition of anti-PD-1 antibody increased the immunogenicity and anti-tumor activity of Ad-CEA vaccination in a murine model of colon cancer. Ad-CEA was administered prior to implantation of MC-38-CEA cells followed by administration of anti-PD-1 antibody. CEA-specific T-cell responses were measured by flow cytometry and ELISPOT. Dynamic co-culture of splenocytes with tumor cells was conducted to analyze anti-tumor activities. Tumor infiltration by lymphocytes was measured by IHC. Tumor volume and overall survival were also recorded. Ad-CEA combined with anti-PD-1 antibody showed greater anti-tumor activity compared with either alone. The combination also increased T-cell infiltration but decreased Tregs. Combining Ad-CEA vaccination with anti-PD-1 antibody enhanced anti-tumor activity and immune responses.
本研究旨在确定抗 PD-1 抗体是否能增强 Ad-CEA 疫苗接种在结直肠癌小鼠模型中的免疫原性和抗肿瘤活性。在 MC-38-CEA 细胞植入前给予 Ad-CEA，然后给予抗 PD-1 抗体。通过流式细胞术和 ELISPOT 测量 CEA 特异性 T 细胞反应。通过动态共培养脾细胞与肿瘤细胞来分析抗肿瘤活性。通过 IHC 测量淋巴细胞浸润肿瘤的情况。还记录了肿瘤体积和总生存期。与单独使用相比，Ad-CEA 联合抗 PD-1 抗体显示出更强的抗肿瘤活性。该组合还增加了 T 细胞浸润，但减少了 Tregs。将 Ad-CEA 疫苗接种与抗 PD-1 抗体联合使用可增强抗肿瘤活性和免疫反应。
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