Zhao Shushu, Wu Shuting, Jiang Sheng, Zhao Gan, Wang Bin
Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China.
Vaccines (Basel). 2023 Aug 5;11(8):1330. doi: 10.3390/vaccines11081330.
Cancer is a major public health threat, and researchers are constantly looking for new ways to develop effective treatments. One approach is the use of cancer vaccines, which work by boosting the body's immune system to fight cancer. The goal of this study was to develop an effective cancer vaccine using rendered-inactive tumor cells. A CMS5 fibrosarcoma tumor model in BALB/c mice and an E.G7 lymphoma tumor model in C57BL/6 mice were used to evaluate how mitomycin C-inactivated tumor cells mediated tumor protection. The results showed that immunization with inactivated CMS5 cells significantly improved tumor suppression after a challenge with live CMS5 tumor cells, but no effect was observed using the E.G7 tumor model. The results suggested that DC (dendritic cell) responses to tumor antigens are critical. The maturation and activation of DCs were effectively promoted by mitomycin C-treated CMS5 cells, as well as enhanced phagocytosis ability in vitro. The tumor-protective effects established by the vaccination of inactivated CMS5 cells were CD8+ T cell-dependent, as the antitumor responses disappeared after eliminating CD8+ T cells. It was found that the tumor-prevention efficacy was dramatically increased by combining inactivated CM55 tumor cells with anti-CD25 antibodies to temporarily deplete Treg cells (regulatory T cells). This strategy could also significantly induce the rejection against E.G7 tumors. In addition, vaccination with anti-CD25 antibodies plus inactivated CMS5 cells elicited antitumor responses against heterologous tumors. According to the findings of this study, combining the immunization of inactivated tumor cells with an anti-CD25 antibody may be an effective method for cancer prevention.
癌症是主要的公共卫生威胁，研究人员一直在不断寻找开发有效治疗方法的新途径。一种方法是使用癌症疫苗，其作用原理是增强机体免疫系统来对抗癌症。本研究的目的是利用经灭活处理的肿瘤细胞开发一种有效的癌症疫苗。采用BALB/c小鼠的CMS5纤维肉瘤肿瘤模型和C57BL/6小鼠的E.G7淋巴瘤肿瘤模型来评估丝裂霉素C灭活的肿瘤细胞介导的肿瘤保护作用。结果显示，用灭活的CMS5细胞免疫可显著提高在受到活的CMS5肿瘤细胞攻击后的肿瘤抑制效果，但在E.G7肿瘤模型中未观察到效果。结果表明，树突状细胞（DC）对肿瘤抗原的反应至关重要。丝裂霉素C处理的CMS5细胞有效促进了DC的成熟和激活，以及体外吞噬能力的增强。灭活的CMS5细胞疫苗接种所建立的肿瘤保护作用依赖于CD8⁺T细胞，因为在清除CD8⁺T细胞后抗肿瘤反应消失。研究发现，将灭活的CM55肿瘤细胞与抗CD25抗体联合使用以暂时耗竭调节性T细胞（Treg细胞）可显著提高肿瘤预防效果。该策略还可显著诱导对E.G7肿瘤的排斥反应。此外，用抗CD25抗体加灭活的CMS5细胞进行疫苗接种可引发针对异源肿瘤的抗肿瘤反应。根据本研究结果，将灭活肿瘤细胞免疫与抗CD25抗体联合使用可能是一种有效的癌症预防方法。
