There are also several PD-1 antibodiesREGN2810, AMP-224, and BGB-A317still in phase I clinical trials. immunotherapy in the pediatric population. strong class=”kwd-title” Keywords: pediatrics, immunotherapy Immune checkpoint inhibitors, which include programmed cell death protein 1 (PD-1)/cell death protein Ophiopogonin D’ ligand 1 (PD-L1), have substantially improved treatment outcomes and achieved a breakthrough in adult cancers in the past few years.1C3 The PD-1 receptor, a transmembrane glycoprotein, plays a crucial role in the immune evasion mechanism which downregulates T-cell activation. The activation of CD8+ T cells is suppressed by the engagement of PD-1 with PD-L1 on tumor cells. Blockade of the PD-1/PD-L1 pathway restores the ability of T cells to target tumor cells. Currently, several immune checkpoint inhibitorsnivolumab, pembrolizumab, avelumab, and toripalimabhave been approved by the Food and Drug Administration, European Medicines Agency, and China Food and Drug Administration for Ophiopogonin D’ use in Ophiopogonin D’ adult cancers. There are also several PD-1 antibodiesREGN2810, AMP-224, and BGB-A317still in phase I clinical trials. The main PD-1 and PD-L1 antibodies are summarized in online supplemental table 1. Supplementary datajitc-2021-002920supp001.pdf Studies of checkpoint inhibitors specifically targeting PD-1/PD-L1 in pediatric patients are limited.4 Results from an interim analysis of the KEYNOTE-051 trial indicated that pembrolizumab had antitumor activity against relapsed or refractory Hodgkins lymphoma (HL) and some uncommon tumor types (mesothelioma and adrenocortical carcinoma).5 In addition, nivolumab was safe and displayed antitumor activity in the pediatric population with relapsed or refractory non-central nervous system (CNS) solid tumors or lymphoma.6 Nevertheless, when used alone, neither nivolumab nor pembrolizumab showed activity in the sporadic pediatric solid tumor histotypes. For non-HL tumors, anti-PD-1 showed modest efficacy, which might be due to the low tumor mutational burden (TMB) or low PD-L1 expression in the tumor microenvironment. Currently, there is significant evidence that combination immunotherapy shows clinical activity compared with PD-1 alone in adult cancer types. However, the status of combination therapy in pediatric cancer remains unknown. Thus, there is still great potential for researchers to explore whether PD-1 monotherapy with or without other regimens is effective in treating pediatric tumors. This commentary provides an assessment of ongoing clinical trials using PD-1 or PD-L1 inhibitors alone or in combination with other therapies and provides specific insights into the methods for conducting clinical trials of immunotherapy in the pediatric population. We first initiated a search on ClinicalTrials. gov on September 8, 2020, using the following search terms: PD-1 OR PD-L1 OR Nivolumab OR Pembrolizumab OR Durvalumab OR Toripalimab OR Sintilimab OR Atezolizumab OR avelumab OR REGN2810 OR AMP-224 OR AMP-514 OR PDR-001 OR BCD-100 OR TSR-042 OR JNJ-63723283 Rabbit Polyclonal to Chk2 (phospho-Thr68) OR PF-0681591 OR BI-754091 OR SHR-1210 OR JS001 OR IBI308 OR GB226 OR GLS-010 OR LZM009 OR HX008 OR BGB-A317 OR M7824 OR CX-072 OR FAZ-053 OR LY-3300054 OR CA-170 OR SHR-1316 OR KN035 OR ZKAB001 OR CS1001 OR BAT1306. Using this search strategy, 2688 trials were identified. We limited trials to ongoing clinical trials in which the status was recruiting or not yet recruiting, and the age of patients enrolled was 18 years. Then, 150 trials were identified to be screened. Next, we excluded 10 duplicate tests, 7 tests that did not involve PD-1 antibody therapy, 1 trial that was not related to tumor therapy, 22 observational tests, and Ophiopogonin D’ 12 tests that did not meet the inclusion age requirements. After exam for manual categorization, 98 tests were selected for review (on-line supplemental table 2). Judging from your analysis, 24 of the 98 interventional tests were related to PD-1/PD-L1 monoclonal antibodies.