CELL INTELLIGENCE · 肿瘤细胞治疗研究

Anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy has dramatically changed the therapeutic landscape of inoperable non-small cell lung cancer (NSCLC), and has been included in first-line treatments. Sintilimab is a domestic anti-PD-1 monoclonal antibody in China that has received approvals from the National Medical Products Administration to treat classical Hodgkin's lymphoma, hepatocellular carcinoma, and squamous and non-squamous NSCLC. In a prospective clinical study we led, neoadjuvant sintilimab has led to major and complete pathologic responses, which are recommended as surrogate endpoints for neoadjuvant immunotherapy; however, its effect remains inconclusive in pulmonary ground glass nodules. Meanwhile, combination plans seem more likely to be satisfying therapeutic options. Specifically, sintilimab plus platinum-based chemotherapy plans conferred better anti-tumor efficacy and clinical benefits compared to chemotherapy alone, which led to their approval in China and the acceptance of a biological license application in the US. Besides, the combination with other plans, such as docetaxel, cytokine-induced killer cell immunotherapy, radiation therapy, and anlotinib have also shown promising anti-tumor efficacy, with acceptable toxicities, and are therefore worth further exploration. In addition, several clinical trials on NSCLC at our center are ongoing. In general, sintilimab and its combinatorial plans were effective and well tolerated, but the treatment requires appropriate timing; pathologic responses can be surrogate endpoints for neoadjuvant immunotherapy, while more effective biomarkers are warranted. This study provides an overview of sintilimab-based clinical trials on NSCLC, and may support further investigation of sintilimab in future clinical trials.