Clinically approved combination immunotherapy: Current status, limitations, and future perspective

Current Research in Immunology

Meixiao Zhan¹  Yong Li²  Jun Jiang³  Danielle J. Dauphars⁴  Sheng Luo⁵  Hua Yin⁵  Xian-Yang Li⁶  Hui Zhang⁶  Shi-You Li⁶  You-Wen He⁶  Ligong Lu⁶ 

[1] Corresponding author. No.79, Kangning Road, Xiangzhou District, Zhuhai, 519000, Guangdong Province, China.;Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 27710, USA;Department of Immunology, Duke University Medical Center, Durham, NC, 27710, USA;First Affiliated Hospital, China Medical University, Shenyang, China;Tricision Biotherapeutic Inc, Jinwan District, Zhuhai, China;Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, Guangdong Province, 519000, PR China;

关键词: Combination immunotherapy;    First-line therapy;    Atezolizumab;    Bevacizumab;    HCC;    Dose;   

DOI  :  

来源: DOAJ

【 摘 要 】

Immune-checkpoint inhibitor-based combination immunotherapy has become a first-line treatment for several major types of cancer including hepatocellular carcinoma (HCC), renal cell carcinoma, lung cancer, cervical cancer, and gastric cancer. Combination immunotherapy counters several immunosuppressive elements in the tumor microenvironment and activates multiple steps of the cancer-immunity cycle. The anti-PD-L1 antibody, atezolizumab, plus the anti-vascular endothelial growth factor antibody, bevacizumab, represents a promising class of combination immunotherapy. This combination has produced unprecedented clinical efficacy in unresectable HCC and become a landmark in HCC therapy. Advanced HCC patients treated with atezolizumab plus bevacizumab demonstrated impressive improvements in multiple clinical endpoints including overall survival, progress-free survival, objective response rate, and patient-reported quality of life when compared to current first-line treatment with sorafenib. However, atezolizumab plus bevacizumab first-line therapy has limitations. First, cancer patients falling into the criteria for the combination therapy may need to be further selected to reap benefits while avoiding some potential pitfalls. Second, the treatment regimen of atezolizumab plus bevacizumab at a fixed dose may require adjustment for optimal normalization of the tumor microenvironment to obtain maximum efficacy and reduce adverse events. Third, utilization of predictive biomarkers is urgently needed to guide the entire treatment process. Here we review the current status of clinically approved combination immunotherapies and the underlying immune mechanisms. We further provide a perspective analysis of the limitations for combination immunotherapies and potential approaches to overcome the limitations.

【 授权许可】

Unknown