用于肿瘤根除和高频纳秒协议的钙电化学疗法及其潜力
Calcium Electrochemotherapy for Tumor Eradication and the Potential of High-Frequency Nanosecond Protocols.
发表日期:2023 Jul 31
作者:
Eivina Radzevičiūtė-Valčiukė, Augustinas Želvys, Eglė Mickevičiūtė, Jovita Gečaitė, Auksė Zinkevičienė, Veronika Malyško-Ptašinskė, Vytautas Kašėta, Jurij Novickij, Tatjana Ivaškienė, Vitalij Novickij
来源:
Cell Death & Disease
摘要:
钙电穿孔(CaEP)是一种创新的治疗癌症的方法,通过电穿孔使超生理量的钙内化,导致细胞死亡。CaEP使化疗药物(例如博莱霉素)得以替代。本研究介绍了用于消除C57BL/6J小鼠癌肿的标准微秒级(μsCaEP)和新型高频纳秒级钙电穿孔(nsCaEP)方案。我们展示了CaEP在体内消除肿瘤并提高其生存率的有效性。治疗后通过调查肿瘤、脾脏、淋巴结和血液中的免疫细胞群体以及评估抗肿瘤抗体来观察抗肿瘤免疫反应。CaEP治疗导致CD4+和CD8+中央记忆T细胞的百分比增加,并减少脾脏的骨髓源性抑制细胞(MDSC)。此外,CaEP治疗后检测到抗肿瘤IgG抗体水平的增加。实验结果表明,给予CaEP治疗导致肿瘤生长延缓、生存率提高,并刺激免疫反应,表明CaEP与免疫疗法之间存在潜在的协同关系。
Calcium electroporation (CaEP) is an innovative approach to treating cancer, involving the internalization of supraphysiological amounts of calcium through electroporation, which leads to cell death. CaEP enables the replacement of chemotherapeutics (e.g., bleomycin). Here, we present a standard microsecond (μsCaEP) and novel high-frequency nanosecond protocols for calcium electroporation (nsCaEP) for the elimination of carcinoma tumors in C57BL/6J mice. We show the efficacy of CaEP in eliminating tumors and increasing their survival rates in vivo. The antitumor immune response after the treatment was observed by investigating immune cell populations in tumors, spleens, lymph nodes, and blood, as well as assessing antitumor antibodies. CaEP treatment resulted in an increased percentage of CD4+ and CD8+ central memory T cells and decreased splenic myeloid-derived suppressor cells (MDSC). Moreover, increased levels of antitumor IgG antibodies after CaEP treatment were detected. The experimental results demonstrated that the administration of CaEP led to tumor growth delay, increased survival rates, and stimulated immune response, indicating a potential synergistic relationship between CaEP and immunotherapy.