Tislelizumab: A Modified Anti-tumor Programmed Death Receptor 1 Antibody

Abstract

Tislelizumab is an anti-programmed death receptor 1 (PD-1) monoclonal immunoglobulin G 4 antibody developed by BeiGene. The structure of tislelizumab has been modified to maximally inhibit the binding of PD-1 to programmed death ligand 1 (PD-L1) and minimize the binding of tislelizumab to Fcγ receptors. In clinical studies, tislelizumab has shown preliminary anti-tumor effects in various solid tumors, such as Hodgkin’s lymphoma, urothelial carcinoma, lung cancer, gastric and esophageal cancer, liver cancer, nasopharyngeal carcinoma, colorectal cancer, and microsatellite instability-high/mismatch repair-deficient tumors. In addition, it also showed new promise in solid tumor treatment in combination with ociperlimab. Due to its satisfactory anti-tumor effects, tislelizumab has received approvals in China for the treatment of classical Hodgkin’s lymphoma, urothelial carcinoma, squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, and hepatocellular carcinoma, and it is now under investigation for a new indication in microsatellite instability-high/mismatch repair-deficient tumors. Moreover, it has been granted orphan designations in hepatocellular carcinoma, esophageal cancer, and gastric cancer, including cancer of the gastroesophageal junction, by the US Food and Drug Administration. Tislelizumab has an acceptable safety profile; the most common adverse effects include fatigue, anemia, and decreased neutrophil count, while the most fatal events have been related to respiratory infection or failure, and hepatic injury. Tislelizumab has an economic advantage compared with other well-studied PD-1/PD-L1 inhibitors; thus, the introduction of it could provide clinical oncologists with an effective weapon against tumors and may alleviate the burden of cancer patients.

Tislelizumab for cervical cancer: A retrospective study and analysis of correlative blood biomarkers

“…Several clinical trials have reported encouraging antitumor activity and manageable TRAEs in patients with advanced solid tumors who underwent tislelizumab treatment ( 25 , 26 ). Furthermore, tislelizumab has been included in the medical insurance catalogue in China, which reduces its price ( 14 ). Thus, it may prove to be an efficient and cost-effective PD-1 inhibitor for the treatment of advanced CC, and this warrants further study.…”

“…Tislelizumab, a humanized immunoglobulin (Ig) G4 monoclonal antibody with high specificity and affinity for PD-1, was engineered to minimize the binding of Fcγ receptors on macrophages. It reduces antibody-dependent phagocytosis, which is thought to be the mechanism underlying T-cell clearance and resistance to anti-PD-1 therapy ( 14 ). Given its favorable antitumor activity and tolerance, tislelizumab has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of esophageal cancer, hepatocellular carcinoma, and gastric/gastroesophageal junction cancer ( 15 ).…”

Tislelizumab for squamous lung cancer combined with basal cell carcinoma of the skin: A case report

“…They can block PD-1/PD-L1 interaction, activate T cells, and restore their anti-tumor immune response. [ 3 ] Tislelizumab [ 4 , 5 ] is a humanized monoclonal antibody against PD-1(IgG4 variant) that was independently developed in China. Its antibody structure differ from that of the traditional PD-1 antibody.…”

“…In recent years, some researchers have tried to use tislelizumab for refractory renal cell carcinoma, cholangiocarcinoma, and serous endometrial carcinoma, all of which have achieved good therapeutic effects. [ 5 ]…”

Case Report: Complete response after tislelizumab treatment in a hepatocellular carcinoma patient with abdominal lymph node metastasis

“…In this study, the efficacy of combination therapy was not evaluated because the patient refused chemotherapy. Tislelizumab, an anti-PD-1 antibody developed in China that has a different structure to that of traditional anti-PD-1 antibodies ( 21 ), produced an ORR of 13% (32/249) in HCC patients regardless of the number of prior lines of treatment ( 22 ). Chao et al.…”