Si Chunfeng, Xu Maolei, Lu Meiyu, Yu Yan, Yang Meizi, Yan Miaomiao, Zhou Ling, Yang Xiaoping
Key Laboratory of Traditional Chinese Medicine Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine, School of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
Medicine and Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong 264003, P.R. China.
Oncol Lett. 2017 Dec;14(6):7391-7397. doi: 10.3892/ol.2017.7169. Epub 2017 Oct 11.
Cancer cell vaccines with strong specificity and low tolerance have been revealed to be a promising option for oncology treatment. Various antigen forms, including tumor cell lysate and glutaraldehyde-fixed tumor cells, have been intensively used in cancer vaccine preparation. However, the most effective antigen form has not yet been identified. In the present study, the antitumor efficiency of vaccines prepared by these two antigen forms was systematically investigated. Murine H22 hepatocellular carcinoma cell lysate and glutaraldehyde-fixed H22 hepatocellular carcinoma cells were conjugated with Freund's adjuvant to prepare vaccines, H22-TCL and Fixed-H22-CELL, respectively. H22-TCL and Fixed-H22-CELL were administrated by subcutaneous immunization in prophylactic and therapeutic strategies. The results of the present study revealed that H22-TCL immunization induced more significant inhibition on tumor growth and metastasis compared with Fixed-H22-CELL injection. Furthermore, histopathological observation demonstrated that H22-TCL vaccine induced larger areas of continuous necrosis within tumors compared to the Fixed-H22-CELL vaccine, which was associated with the extent of tumor inhibition. More importantly, the H22-TCL vaccine injection elicited more evident antigen-specific antibody responses compared with the Fixed-H22-CELL injection. Splenocytes from H22-TCL vaccinated mice also exhibited a more significant T lymphocytes proliferation compared with that from Fixed-H22-CELL-treated mice. All the results indicated that whole tumor cell lysate may be a more effective antigen form in cancer vaccine preparation compared with glutaraldehyde-fixed tumor cells, which elicited more marked antigen specific humoral and cellular immune responses resulted with a superior antitumor efficiency. This would have important clinical signification for cancer vaccine preparation and serve a role in prompting this to other researchers.
具有强特异性和低耐受性的癌细胞疫苗已被证明是肿瘤治疗的一个有前景的选择。包括肿瘤细胞裂解物和戊二醛固定的肿瘤细胞在内的各种抗原形式已被广泛用于癌症疫苗制备。然而，最有效的抗原形式尚未确定。在本研究中，系统地研究了由这两种抗原形式制备的疫苗的抗肿瘤效果。将小鼠H22肝癌细胞裂解物和戊二醛固定的H22肝癌细胞分别与弗氏佐剂结合制备疫苗，即H22-TCL和Fixed-H22-CELL。H22-TCL和Fixed-H22-CELL通过皮下免疫用于预防和治疗策略。本研究结果表明，与注射Fixed-H22-CELL相比，H22-TCL免疫对肿瘤生长和转移的抑制作用更显著。此外，组织病理学观察表明，与Fixed-H22-CELL疫苗相比，H22-TCL疫苗诱导肿瘤内更大面积的连续坏死，这与肿瘤抑制程度相关。更重要的是，与注射Fixed-H22-CELL相比，注射H22-TCL疫苗引发更明显的抗原特异性抗体反应。与Fixed-H22-CELL处理的小鼠相比，接种H22-TCL疫苗的小鼠脾细胞也表现出更显著的T淋巴细胞增殖。所有结果表明，与戊二醛固定的肿瘤细胞相比，全肿瘤细胞裂解物可能是癌症疫苗制备中更有效的抗原形式，其引发更显著的抗原特异性体液和细胞免疫反应，具有更高的抗肿瘤效率。这对癌症疫苗制备具有重要的临床意义，并为其他研究人员起到推动作用。
