Monitoring CAR‐T cell kinetics in clinical trials by multiparametric flow cytometry: Benefits and challenges
Autor: | Reinhold Pollner, Ghanashyam Sarikonda, Kevin Nguyen, Anil Pahuja, Creton Kalfoglou, Kerri Burns, Naveen Dakappagari, Irene L. Ch’en, Shabnam Tangri |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Clinical Trials as Topic Receptors Chimeric Antigen Histology medicine.diagnostic_test business.industry T-Lymphocytes Cell Biology Computational biology Flow Cytometry Immunotherapy Adoptive Chimeric antigen receptor Pathology and Forensic Medicine Flow cytometry Clinical trial Cellular kinetics Kinetics 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis medicine Humans Car t cells business |
Zdroj: | Cytometry Part B: Clinical Cytometry. 100:72-78 |
ISSN: | 1552-4957 1552-4949 |
Popis: | Exceptional clinical responses produced by the first chimeric antigen receptor T [CAR-T] cell therapies, and their entry into commercial markets prompted a logarithmic increase in the number of next generation CAR-T clinical trials. As a result, there is a growing interest in understanding the analytical approaches utilized for reliable monitoring of these "living" drugs, and the challenges encountered during their clinical development. Multiparametric flow cytometry (MFC) assays have played a crucial role in understanding the phenotype and function of first approved CAR-T therapies. Herein, three main areas for monitoring CAR-T therapies in clinical trials are discussed: (1) analytical considerations critical for development of MFC assays for the reliable enumeration of CAR-T levels, (2) operational challenges associated with clinical trial sampling and transportation, and (3) differential cellular kinetics observed by MFC and qPCR analyses and their relationship with efficacy (measurable residual disease levels). Initial experiences described here may enable design of fit-for-purpose tools and help to more rapidly advance the development of next generation CAR-T therapies. |
Databáze: | OpenAIRE |
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