CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Progress and challenges of immunotherapy in triple-negative breast cancer.
Progress and challenges of immunotherapy in triple-negative breast cancer.
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三阴性乳腺癌(TNBC)是乳腺癌的一种亚型,其定义为缺乏雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)表达。与乳腺癌其他亚型相比,TNBC更易复发和转移,生存率较低。由于缺乏明确靶点,过去数十年新型治疗手段有限,化疗仍是主要治疗方式。随着免疫检查点抑制(ICI)在实体瘤中的发展以及TNBC免疫原性的验证,免疫治疗日益受到关注。基于不断积累的临床研究,本文综述了TNBC不同治疗线次中针对各类免疫检查点的进展,包括程序性死亡受体1(PD-1)/程序性死亡配体1(PD-L1)抑制剂、细胞毒性T淋巴细胞相关抗原4(CTLA-4)抑制剂,以及其他新型免疫治疗方法,例如个体化肽疫苗、癌睾抗原、新抗原疫苗、RNA疫苗和嵌合抗原受体修饰T细胞(CAR-T)。为改善TNBC患者的生存结局,本文还讨论了免疫治疗的潜在预测生物标志物(如PD-L1表达、肿瘤突变负荷、TIL(肿瘤浸润淋巴细胞)、微卫星不稳定性/错配修复缺陷)及未来治疗面临的挑战。
Triple-negative breast cancer (TNBC), a subtype of breast cancer, is defined as lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) expression. Compared with other subtypes in breast cancer, TNBC is more likely to recur and metastasize, with a lower survival rate. Due to the absence of definitive targets, there was limited novel therapeutic interventions and chemotherapy remained the primary treatment in the past decades. Following the development of immune checkpoint inhibition (ICI) in solid tumors and validation of the immunogenicity in TNBC, immunotherapy has attracted more and more attentions.
On basis of accumulating clinical studies, we reviewed the current progress targeting different immune checkpoints in several-lines treatment for TNBC, including programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) inhibitor, and other novel immunotherapeutic approaches (e. g.
, individualized peptide vaccine, cancer-testis antigen (CTA), new antigen vaccine, RNA vaccine and chimeric antigen receptor modified T cells (CAR-T)). In order to improve the survival outcome of TNBC populations, we further discussed potential predictive biomarkers for immunotherapy (e. g. , PD-L1 expression, tumor mutational burden (TMB), tumor-infiltrating lymphocytes (TILs), microsatellite instability (MSI)/mismatch repair (MMR) deficiency) and challenges in the future treatment of TNBC.
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