Lu Chenyu, Tan Yuanyan
Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong SAR, China.
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China.
Mol Ther Oncol. 2024 Feb 12;32(1):200773. doi: 10.1016/j.omton.2024.200773. eCollection 2024 Mar 21.
Immune checkpoint inhibitors (ICIs) have shown great promise as immunotherapy for restoring T cell function and reactivating anti-tumor immunity. The US Food and Drug Administration (FDA) approved the first immune checkpoint inhibitor, ipilimumab, in 2011 for advanced melanoma patients, leading to significant improvements in survival rates. Subsequently, other immune checkpoint-targeting antibodies were tested. Currently, seven ICIs, namely ipilimumab (anti-cytotoxic T lymphocyte-associated protein 4 [CTLA4]), pembrolizumab, nivolumab (anti-programmed cell death protein 1 [PD-1]), atezolizumab, avelumab, durvalumab, and cemiplimab (anti-PD-L1), have been approved for various cancer types. However, the efficacy of antibodies targeting CTLA4 or PD-1/programmed death-ligand 1 (PD-L1) remains suboptimal. Consequently, ongoing studies are evaluating the next generation of ICIs, such as lymphocyte activation gene-3 (LAG3), T cell immunoglobulin and mucin-domain containing 3 (TIM3), and T cell immunoglobulin and ITIM domain (TIGIT). Our review provides a summary of clinical trials evaluating these novel immune checkpoints in cancer treatment.
免疫检查点抑制剂(ICIs)作为一种免疫疗法,在恢复T细胞功能和重新激活抗肿瘤免疫方面显示出巨大的潜力。2011年,美国食品药品监督管理局(FDA)批准了首个免疫检查点抑制剂伊匹单抗用于晚期黑色素瘤患者,显著提高了生存率。随后,对其他靶向免疫检查点的抗体进行了测试。目前,七种ICIs,即伊匹单抗(抗细胞毒性T淋巴细胞相关蛋白4 [CTLA4])、帕博利珠单抗、纳武利尤单抗(抗程序性细胞死亡蛋白1 [PD-1])、阿替利珠单抗、阿维鲁单抗、度伐利尤单抗和西米普利单抗(抗PD-L1),已被批准用于多种癌症类型。然而,靶向CTLA4或PD-1/程序性死亡配体1(PD-L1)的抗体疗效仍不理想。因此,正在进行的研究正在评估下一代ICIs,如淋巴细胞激活基因-3(LAG3)、含T细胞免疫球蛋白和粘蛋白结构域3(TIM3)以及含T细胞免疫球蛋白和ITIM结构域(TIGIT)。我们的综述总结了评估这些新型免疫检查点在癌症治疗中应用的临床试验。