PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Enhancing Dendritic Cell Cancer Vaccination: The Synergy of Immune Checkpoint Inhibitors in Combined Therapies.
Enhancing Dendritic Cell Cancer Vaccination: The Synergy of Immune Checkpoint Inhibitors in Combined Therapies.
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树突状细胞(DC)癌症疫苗是一种有前景的治疗方法,利用免疫系统对抗肿瘤。这些疫苗利用DC将肿瘤相关抗原呈递给T细胞的能力,触发强烈的免疫反应。DC疫苗的开发已经经历了三代。第一代涉及在体外用肿瘤相关抗原或信使RNA致敏DC,临床成功率有限。第二代通过使用细胞因子混合物和专门的DC亚群来增强免疫原性,提高了疗效。第三代使用血液来源的DC来引发更强的免疫反应。临床试验表明,癌症疫苗的毒性低于传统的细胞毒性治疗。
然而,利用DC免疫疗法实现显著的临床反应仍然具有挑战性。将DC疫苗与免疫检查点抑制剂(ICIs),如抗细胞毒性T淋巴细胞抗原4和抗程序性死亡-1抗体,联合使用已显示出前景,通过增强T细胞反应和改善临床结果。这些联合方案可以将非炎症性肿瘤转化为炎症性肿瘤,增强ICIs的疗效。当前研究正在探索新的检查点靶点,如LAG-3、TIM-3和TIGIT,考虑它们与DC疫苗的潜力。
此外,用嵌合抗原受体或T细胞受体工程化T细胞可以进一步增强抗肿瘤反应。这种综合策略旨在增强癌症免疫疗法,重点关注提高疗效和改善患者生存率。
Dendritic cell (DC) cancer vaccines are a promising therapeutic approach, leveraging the immune system to fight tumors. These vaccines utilize DCs' ability to present tumor-associated antigens to T cells, triggering a robust immune response. DC vaccine development has progressed through three generations. The first generation involved priming DCs with tumor-associated antigens or messenger RNA outside the body, showing limited clinical success.
The second generation improved efficacy by using cytokine mixtures and specialized DC subsets to enhance immunogenicity. The third generation used blood-derived DCs to elicit a stronger immune response. Clinical trials indicate that cancer vaccines have lower toxicity than traditional cytotoxic treatments.
However, achieving significant clinical responses with DC immunotherapy remains challenging. Combining DC vaccines with immune checkpoint inhibitors (ICIs), such as anticytotoxic T-lymphocyte Antigen 4 and antiprogrammed death-1 antibodies, has shown promise by enhancing T-cell responses and improving clinical outcomes. These combinations can transform non-inflamed tumors into inflamed ones, boosting ICIs' efficacy. Current research is exploring new checkpoint targets like LAG-3, TIM-3, and TIGIT, considering their potential with DC vaccines.
Additionally, engineering T cells with chimeric antigen receptors or T-cell receptors could further augment the antitumor response. This comprehensive strategy aims to enhance cancer immunotherapy, focusing on increased efficacy and improved patient survival rates.
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