基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:DNA damage response and neoantigens: A favorable target for triple-negative breast cancer immunotherapy and vaccine development.
DNA damage response and neoantigens: A favorable target for triple-negative breast cancer immunotherapy and vaccine development.
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三阴性乳腺癌(TNBC)因其侵袭性强且治疗选择有限,构成了重大的临床挑战。DNA损伤应答(DDR)机制与新抗原出现之间的相互作用,为开发针对TNBC的靶向免疫治疗策略和疫苗提供了有前景的途径。DDR是一个复杂的细胞机制网络,旨在维持基因组完整性。在TNBC中,遗传不稳定性是其标志性特征,DDR组分的失调在肿瘤发生和进展中发挥关键作用。本综述探讨了DDR与新抗原之间的复杂关系,揭示了TNBC细胞潜在的脆弱性。新抗原源于癌细胞中的体细胞突变,代表可被免疫系统识别的独特抗原。TNBC倾向于基因组不稳定性,导致突变负荷增加,从而产生丰富的新抗原库。DDR与新抗原在TNBC中的交汇为免疫治疗靶向提供了独特的机会。免疫治疗通过利用免疫系统选择性靶向癌细胞,彻底改变了癌症治疗。TNBC中DDR相关新抗原所赋予的独特免疫原性,使其成为免疫治疗干预的理想靶点。本综述还探讨了多种免疫治疗模式,包括免疫检查点抑制剂(ICIs)、过继细胞疗法和癌症疫苗,这些模式利用DDR与新抗原的相互作用来增强抗肿瘤免疫应答。
此外,开发针对DDR相关新抗原的疫苗的可能性,为TNBC的预防和治疗策略开辟了新前沿。针对TNBC个体突变图谱合理设计疫苗,为精准医学方法带来了希望。
总之,DDR与新抗原在TNBC中的汇聚为开发创新性免疫疗法和疫苗提供了有力依据。理解并靶向这些相互关联的过程,可能为个性化且有效的干预措施铺平道路,为应对TNBC所带来挑战的患者带来新希望。
Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its aggressive nature and limited therapeutic options. The interplay between DNA damage response (DDR) mechanisms and the emergence of neoantigens represents a promising avenue for developing targeted immunotherapeutic strategies and vaccines for TNBC. The DDR is a complex network of cellular mechanisms designed to maintain genomic integrity. In TNBC, where genetic instability is a hallmark, dysregulation of DDR components plays a pivotal role in tumorigenesis and progression. This review explores the intricate relationship between DDR and neoantigens, shedding light on the potential vulnerabilities of TNBC cells. Neoantigens, arising from somatic mutations in cancer cells, represent unique antigens that can be recognized by the immune system.
TNBC's propensity for genomic instability leads to an increased mutational burden, consequently yielding a rich repertoire of neoantigens. The convergence of DDR and neoantigens in TNBC offers a distinctive opportunity for immunotherapeutic targeting. Immunotherapy has revolutionized cancer treatment by harnessing the immune system to selectively target cancer cells.
The unique immunogenicity conferred by DDR-related neoantigens in TNBC positions them as ideal targets for immunotherapeutic interventions. This review also explores various immunotherapeutic modalities, including immune checkpoint inhibitors (ICIs), adoptive cell therapies, and cancer vaccines, that leverage the DDR and neoantigen interplay to enhance anti-tumor immune responses.
Moreover, the potential for developing vaccines targeting DDR-related neoantigens opens new frontiers in preventive and therapeutic strategies for TNBC. The rational design of vaccines tailored to the individual mutational landscape of TNBC holds promise for precision medicine approaches.
In conclusion, the convergence of DDR and neoantigens in TNBC presents a compelling rationale for the development of innovative immunotherapies and vaccines. Understanding and targeting these interconnected processes may pave the way for personalized and effective interventions, offering new hope for patients grappling with the challenges posed by TNBCs.
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