Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer

IF 29.5 1区 医学 Q1 HEMATOLOGY
Weishi Cheng, Kai Kang, Ailin Zhao, Yijun Wu
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引用次数: 0

Abstract

Cancer immunotherapies, represented by immune checkpoint inhibitors (ICIs), have reshaped the treatment paradigm for both advanced non-small cell lung cancer and small cell lung cancer. Programmed death receptor-1/programmed death receptor ligand-1 (PD-1/PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are some of the most common and promising targets in ICIs. Compared to ICI monotherapy, which occasionally demonstrates treatment resistance and limited efficacy, the dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 operates at different stages of T cell activation with synergistically enhancing immune responses against cancer cells. This emerging dual therapy heralds a new direction for cancer immunotherapy, which, however, may increase the risk of drug-related adverse reactions while improving efficacy. Previous clinical trials have explored combination therapy strategy of anti-PD-1/PD-L1 and anti-CTLA-4 agents in lung cancer, yet its efficacy remains to be unclear with the inevitable incidence of immune-related adverse events. The recent advent of bispecific antibodies has made this sort of dual targeting more feasible, aiming to alleviate toxicity without compromising efficacy. Thus, this review highlights the role of dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in treating lung cancer, and further elucidates its pre-clinical mechanisms and current advancements in clinical trials. Besides, we also provide novel insights into the potential combinations of dual blockade therapies with other strategies to optimize the future treatment mode for lung cancer.
针对肺癌 PD-1/PD-L1 和 CTLA-4 的双重阻断免疫疗法
以免疫检查点抑制剂(ICIs)为代表的癌症免疫疗法重塑了晚期非小细胞肺癌和小细胞肺癌的治疗模式。程序性死亡受体-1/程序性死亡受体配体-1(PD-1/PD-L1)和细胞毒性 T 淋巴细胞相关抗原-4(CTLA-4)是 ICIs 中最常见、最有前景的靶点。ICI 单药治疗偶尔会出现耐药性,疗效有限,相比之下,针对 PD-1/PD-L1 和 CTLA-4 的双重阻断免疫疗法可在 T 细胞活化的不同阶段发挥作用,协同增强针对癌细胞的免疫反应。这种新兴的双重疗法预示着癌症免疫疗法的新方向,但在提高疗效的同时可能会增加药物相关不良反应的风险。之前的临床试验探索了抗PD-1/PD-L1和抗CTLA-4药物在肺癌中的联合治疗策略,但其疗效仍不明确,免疫相关不良反应的发生率也不可避免。最近出现的双特异性抗体使这种双靶向治疗变得更加可行,旨在减轻毒性的同时不影响疗效。因此,本综述强调了以 PD-1/PD-L1 和 CTLA-4 为靶点的双阻断免疫疗法在治疗肺癌中的作用,并进一步阐明了其临床前机制和目前的临床试验进展。此外,我们还对双阻断疗法与其他策略的潜在组合提供了新的见解,以优化未来的肺癌治疗模式。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
48.10
自引率
2.10%
发文量
169
审稿时长
6-12 weeks
期刊介绍: The Journal of Hematology & Oncology, an open-access journal, publishes high-quality research covering all aspects of hematology and oncology, including reviews and research highlights on "hot topics" by leading experts. Given the close relationship and rapid evolution of hematology and oncology, the journal aims to meet the demand for a dedicated platform for publishing discoveries from both fields. It serves as an international platform for sharing laboratory and clinical findings among laboratory scientists, physician scientists, hematologists, and oncologists in an open-access format. With a rapid turnaround time from submission to publication, the journal facilitates real-time sharing of knowledge and new successes.
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