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Review
. 2021 Jan;100(1):72-78.
doi: 10.1002/cyto.b.21891. Epub 2020 Jun 23.

Monitoring CAR-T cell kinetics in clinical trials by multiparametric flow cytometry: Benefits and challenges

Ghanashyam Sarikonda  1 , Anil Pahuja  1 , Creton Kalfoglou  2 , Kerri Burns  1 , Kevin Nguyen  1 , Irene L Ch'en  1 , Reinhold Pollner  1 , Shabnam Tangri  1 , Naveen Dakappagari  1
Affiliations
Free article
Review

Monitoring CAR-T cell kinetics in clinical trials by multiparametric flow cytometry: Benefits and challenges

Ghanashyam Sarikonda et al. Cytometry B Clin Cytom. 2021 Jan.
Free article

Abstract

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.

Keywords: CAR-T; cellular kinetics; critical reagents; flow cytometry; validation.

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References

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