使用 MAGE-A3 mRNA 癌症疫苗进行创新癌症免疫疗法。
Innovative Cancer Immunotherapy with MAGE-A3 mRNA Cancer Vaccines.
发表日期:2024 Oct 09
作者:
Kangchan Choi, Hyorim Jeong, Do Hyun Lee, Ji Won Lee, Ju-Eun Hong, Jin Ee Baek, Yong Serk Park
来源:
Cancers
摘要:
癌症每年在全球造成超过 1000 万人死亡,仍然是一项重大的全球健康挑战。这项研究调查了先进的免疫治疗策略,重点关注针对肿瘤特异性抗原以激活免疫系统的 mRNA 疫苗。我们开发了一种新型 mRNA 疫苗,使用 O,O'-二肉豆蔻基-N-赖氨酰天冬氨酸 (DMKD) 来提高稳定性,并使用磷脂酰丝氨酸 (PS) 来增强免疫细胞的抗原呈递。该疫苗含有封装在脂质纳米颗粒 (LNP) 内的黑色素瘤相关抗原 A3 (MAGE-A3) mRNA,评估了其对抗结直肠癌的治疗潜力。我们的研究结果表明,含有 MAGE-A3 mRNA 的 DMKD-PS LNP 显着减小了肿瘤的大小和重量,有效对抗转移性癌症。该疫苗引发了强烈的免疫反应,增加了特异性免疫球蛋白和细胞因子的水平,而不会引起主要器官的组织毒性。这些结果证实基于 DMKD-PS 的 MAGE-A3 mRNA 疫苗有望用于癌症预防和治疗。
Cancer causes over 10 million deaths annually worldwide and remains a significant global health challenge. This study investigated advanced immunotherapy strategies, focusing on mRNA vaccines that target tumor-specific antigens to activate the immune system. We developed a novel mRNA vaccine using O,O'-dimyristyl-N-lysyl aspartate (DMKD) to improve stability and phosphatidylserine (PS) to enhance antigen presentation to immune cells. This vaccine, containing melanoma-associated antigen A3 (MAGE-A3) mRNA encapsulated within lipid nanoparticles (LNPs), was evaluated for its therapeutic potential against colorectal cancer. Our findings demonstrated that MAGE-A3 mRNA-containing DMKD-PS LNPs significantly reduced tumor size and weight, effectively combating metastatic cancer. The vaccine elicited a robust immune response, increasing specific immunoglobulin and cytokine levels without causing histotoxicity in major organs. These results confirm that the DMKD-PS-based MAGE-A3 mRNA vaccine holds promise for cancer prevention and treatment.