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:The current status of immunotherapy and future horizon in the treatment of metastatic and locally advanced gastroesophageal adenocarcinoma.
The current status of immunotherapy and future horizon in the treatment of metastatic and locally advanced gastroesophageal adenocarcinoma.
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GEA 表现出具有异质性表达的中间免疫原性特征,而 anti-PD-(L)1 治疗的应答者大多富集于具有特定基因组特征的患者,如 MSI-H、高 PD-L1 表达、高 TMB 和 EBV 相关型。
引言:PD-1阻断联合免疫化疗已成为转移性胃及食管腺癌(mGEA)患者当前的一线标准治疗。回顾临床试验发展历程,有助于了解mGEA免疫肿瘤学的演变,并为未来进展奠定基础。综述范围:本文总结了转移性及局部晚期胃及食管腺癌(GEA)免疫治疗既往临床试验结果,并介绍旨在应对当前临床难题的进行中试验。专家观点:总体而言,GEA具有中等免疫原性特征,且表达异质;抗PD-(L)1治疗应答者主要富集于具有特定基因组特征的患者,例如微卫星高度不稳定(MSI-H)、PD-L1高表达、肿瘤突变负荷(TMB)高及EBV相关亚型。正在探索联合抗血管生成药物或同时阻断多个免疫检查点,以使更多患者受益。作者期待CLDN18.2及FGFR2b等新兴靶点能够补充mGEA免疫治疗的治疗空白。双特异性抗体、抗体药物偶联物、CAR-T 及疫苗有望增强疗效并拓展免疫治疗范围。
INTRODUCTION: Immunochemotherapy with PD-1 blockade has been established as the current standard first-line therapy for patients with mGEA. Reviewing the history of clinical trials offers valuable insight into the evolution of immune oncology in mGEA, paving the way for future advancements in this field. AREAS COVERED: This review summarizes the findings of previous clinical trials related to immunotherapy for patients with GEA in the metastatic and locally advanced setting.
We also introduce ongoing clinical trials to address the current challenging issues in clinical practice. EXPERT OPINION: In general, GEA exhibits intermediate immunogenic characteristics with heterogeneous expressions, and responders to anti-PD-(L)1 therapy are mostly enriched to patients with specific genomic profiles such as MSI-H, high PD-L1 expression, high TMB, and EBV-associated type.
Co-administration with anti-angiogenic agents or simultaneous blockade of immune checkpoint molecules is being explored to offer benefit of immunotherapy for more patients.
We hope that CLDN18. 2 and upcoming targets like FGFR2b will complement the treatment niche of immunotherapy in the field of mGEA. Bispecific antibodies, antibody drug conjugates, CAR-T, and vaccine are anticipated to enhance efficacy and expand the scope of immunotherapy.
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