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Monitoring CAR‐T cell kinetics in clinical trials by multiparametric flow cytometry: Benefits and challenges
Author(s) -
Sarikonda Ghanashyam,
Pahuja Anil,
Kalfoglou Creton,
Burns Kerri,
Nguyen Kevin,
Ch'en Irene L.,
Pollner Reinhold,
Tangri Shabnam,
Dakappagari Naveen
Publication year - 2021
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.21891
Subject(s) - chimeric antigen receptor , clinical trial , flow cytometry , medicine , t cell , computational biology , immunology , computer science , biology , pathology , immune system
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.