De Angelis Biagio, D'Amore Maria Luisa, Lecot Pacôme, Neininger Kerstin, Lorrain Margot, Gambotti Laetitia, Dreuillet Caroline, Courcault Elise, Chatterjee Sampurna, Delgado Julio, Galy Anne, Franz Paul, Rodriguez-Madoz Juan Roberto, Cabrerizo Yolanda, Richter Anne, Girvalaki Charis, Noviello Maddalena, Tassi Elena, Sanges Carmen, Luu Maik, Hudecek Michael, Kremer Andreas, Locatelli Franco, Negre Helene, Quintarelli Concetta
Department of Oncology-Haematology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Department of Clinical Research, Institute National du Cancer (French National Cancer Institute-INCa), Boulogne-Billancourt, France.
Front Immunol. 2025 Apr 24;16:1567582. doi: 10.3389/fimmu.2025.1567582. eCollection 2025.
Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a revolutionary approach to cancer treatment. Given the rapid expansion of new indications addressed by newly developed CAR T-cell products, it is essential to standardize analytical methods for the characterization/monitoring of apheresis materials, drug products, and post-infusion patient samples.
The T2Evolve Consortium, part of the European Union's Innovative Medicines Initiative (IMI), conducted an extensive anonymous online survey between February and June 2022. Comprising 36 questions, the survey targeted a wide range of stakeholders involved in engineered T-cell therapies, including researchers, manufacturers, and clinicians. Its goal was to address the current variability within the CAR T-cell field, focusing on analytical assays for quality control of apheresis materials, drug products, and post-infusion immunomonitoring. Another objective was to identify gaps and needs in the field.
A total of 53 respondents from 13 european countries completed the survey, providing insights into the most commonly used assays for apheresis material and drug product characterization, alongside safety and efficacy tests required by the Pharmacopeia. Notably, a minority of respondents conducted phenotypical characterization of T-cell subsets in the drug product and assessed activation/exhaustion T cell profiles.
The survey underscored the necessity to standardize CAR T-cell functional potency assays and identify predictive biomarkers for response, relapse, and toxicity. Additionally, responses indicated significant variability in CAR T-cell monitoring during short-term patient follow-up across clinical centers. This European survey represents the first initiative to report current approaches in different stages of CAR T-cell therapies via a survey, from drug product quality controls to post-infusion immunomonitoring. Based on these findings, and with input from T2EVOLVE experts, the next step will be to address harmonization in the identified areas. These efforts are anticipated to significantly enhance cancer patients' access to engineered T cell therapy safely and effectively throughout Europe.
嵌合抗原受体（CAR）T细胞疗法已成为一种革命性的癌症治疗方法。鉴于新开发的CAR T细胞产品所涉及的新适应症迅速增加，标准化用于单采材料、药品和输注后患者样本的表征/监测的分析方法至关重要。
T2Evolve联盟是欧盟创新药物倡议（IMI）的一部分，于2022年2月至6月进行了一项广泛的匿名在线调查。该调查包含36个问题，目标受众是参与工程化T细胞疗法的广泛利益相关者，包括研究人员、制造商和临床医生。其目的是解决CAR T细胞领域当前的变异性问题，重点关注单采材料、药品的质量控制分析测定以及输注后免疫监测。另一个目标是识别该领域的差距和需求。
来自13个欧洲国家的53名受访者完成了调查，提供了有关单采材料和药品表征最常用测定方法以及药典要求的安全性和有效性测试的见解。值得注意的是，少数受访者对药品中的T细胞亚群进行了表型表征，并评估了T细胞活化/耗竭谱。
该调查强调了标准化CAR T细胞功能效价测定以及识别反应、复发和毒性预测生物标志物的必要性。此外，调查结果表明，在临床中心对患者的短期随访期间，CAR T细胞监测存在显著差异。这项欧洲调查是首次通过调查报告CAR T细胞疗法不同阶段当前方法的举措，从药品质量控制到输注后免疫监测。基于这些发现，并在T2EVOLVE专家的意见基础上，下一步将是解决已确定领域的协调问题。预计这些努力将显著提高欧洲癌症患者安全有效地获得工程化T细胞疗法的机会。
