CAR T-cell detection scoping review: an essential biomarker in critical need of standardization
The expansion and persistence of chimeric antigen receptor (CAR) T-cells in patients are associated with response, toxicity, and long-term efficacy. As such, the tools used to detect CAR T-cells following infusion are fundamental for optimizing this therapeutic approach. Nevertheless, despite the cr...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2023-05-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/5/e006596.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861001305456640 |
|---|---|
| author | Naomi Taylor Nirali N Shah David P Turicek Victoria M Giordani Josquin Moraly |
| author_facet | Naomi Taylor Nirali N Shah David P Turicek Victoria M Giordani Josquin Moraly |
| author_sort | Naomi Taylor |
| collection | DOAJ |
| description | The expansion and persistence of chimeric antigen receptor (CAR) T-cells in patients are associated with response, toxicity, and long-term efficacy. As such, the tools used to detect CAR T-cells following infusion are fundamental for optimizing this therapeutic approach. Nevertheless, despite the critical value of this essential biomarker, there is significant variability in CAR T-cell detection methods as well as the frequency and intervals of testing. Furthermore, heterogeneity in the reporting of quantitative data adds layers of complexity that limit intertrial and interconstruct comparisons. We sought to assess the heterogeneity of CAR T-cell expansion and persistence data in a scoping review using the PRISMA-ScR checklist. Focusing on 21 clinical trials from the USA, featuring a Food and Drug Administration-approved CAR T-cell construct or one of its predecessors, 105 manuscripts were screened and 60 were selected for analysis, based on the inclusion of CAR T-cell expansion and persistence data. Across the array of CAR T-cell constructs, flow cytometry and quantitative PCR were identified as the two primary techniques for detecting CAR T-cells. However, despite apparent uniformity in detection techniques, the specific methods used were highly variable. Detection time points and the number of evaluated time points also ranged markedly and quantitative data were often not reported. To evaluate whether subsequent manuscripts from a trial resolved these issues, we analyzed all subsequent manuscripts reporting on the 21 clinical trials, recording all expansion and persistence data. While additional detection techniques–including droplet digital PCR, NanoString, and single-cell RNA sequencing–were reported in follow-up publications, inconsistencies with respect to detection time points and frequency remained, with a significant amount of quantitative data still not readily available. Our findings highlight the critical need to establish universal standards for reporting on CAR T-cell detection, especially in early phase studies. The current reporting of non-interconvertible metrics and limited provision of quantitative data make cross-trial and cross-CAR T-cell construct comparisons extremely challenging. Establishing a standardized approach for collecting and reporting data is urgently needed and would represent a substantial advancement in the ability to improve outcomes for patients receiving CAR T-cell therapies. |
| format | Article |
| id | doaj-art-f9e49f10d3de42d1b40358e956a1a353 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2023-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-f9e49f10d3de42d1b40358e956a1a3532025-02-10T08:00:11ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-05-0111510.1136/jitc-2022-006596CAR T-cell detection scoping review: an essential biomarker in critical need of standardizationNaomi Taylor0Nirali N Shah1David P Turicek2Victoria M Giordani3Josquin Moraly41 Department of Paediatrics, James Cook University Hospital, Middlesbrough, UKNIH, Bethesda, Maryland, USA6Washington University in St. Louis, St. Louis, MO, USAPediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USAPediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USAThe expansion and persistence of chimeric antigen receptor (CAR) T-cells in patients are associated with response, toxicity, and long-term efficacy. As such, the tools used to detect CAR T-cells following infusion are fundamental for optimizing this therapeutic approach. Nevertheless, despite the critical value of this essential biomarker, there is significant variability in CAR T-cell detection methods as well as the frequency and intervals of testing. Furthermore, heterogeneity in the reporting of quantitative data adds layers of complexity that limit intertrial and interconstruct comparisons. We sought to assess the heterogeneity of CAR T-cell expansion and persistence data in a scoping review using the PRISMA-ScR checklist. Focusing on 21 clinical trials from the USA, featuring a Food and Drug Administration-approved CAR T-cell construct or one of its predecessors, 105 manuscripts were screened and 60 were selected for analysis, based on the inclusion of CAR T-cell expansion and persistence data. Across the array of CAR T-cell constructs, flow cytometry and quantitative PCR were identified as the two primary techniques for detecting CAR T-cells. However, despite apparent uniformity in detection techniques, the specific methods used were highly variable. Detection time points and the number of evaluated time points also ranged markedly and quantitative data were often not reported. To evaluate whether subsequent manuscripts from a trial resolved these issues, we analyzed all subsequent manuscripts reporting on the 21 clinical trials, recording all expansion and persistence data. While additional detection techniques–including droplet digital PCR, NanoString, and single-cell RNA sequencing–were reported in follow-up publications, inconsistencies with respect to detection time points and frequency remained, with a significant amount of quantitative data still not readily available. Our findings highlight the critical need to establish universal standards for reporting on CAR T-cell detection, especially in early phase studies. The current reporting of non-interconvertible metrics and limited provision of quantitative data make cross-trial and cross-CAR T-cell construct comparisons extremely challenging. Establishing a standardized approach for collecting and reporting data is urgently needed and would represent a substantial advancement in the ability to improve outcomes for patients receiving CAR T-cell therapies.https://jitc.bmj.com/content/11/5/e006596.full |
| spellingShingle | Naomi Taylor Nirali N Shah David P Turicek Victoria M Giordani Josquin Moraly CAR T-cell detection scoping review: an essential biomarker in critical need of standardization Journal for ImmunoTherapy of Cancer |
| title | CAR T-cell detection scoping review: an essential biomarker in critical need of standardization |
| title_full | CAR T-cell detection scoping review: an essential biomarker in critical need of standardization |
| title_fullStr | CAR T-cell detection scoping review: an essential biomarker in critical need of standardization |
| title_full_unstemmed | CAR T-cell detection scoping review: an essential biomarker in critical need of standardization |
| title_short | CAR T-cell detection scoping review: an essential biomarker in critical need of standardization |
| title_sort | car t cell detection scoping review an essential biomarker in critical need of standardization |
| url | https://jitc.bmj.com/content/11/5/e006596.full |
| work_keys_str_mv | AT naomitaylor cartcelldetectionscopingreviewanessentialbiomarkerincriticalneedofstandardization AT niralinshah cartcelldetectionscopingreviewanessentialbiomarkerincriticalneedofstandardization AT davidpturicek cartcelldetectionscopingreviewanessentialbiomarkerincriticalneedofstandardization AT victoriamgiordani cartcelldetectionscopingreviewanessentialbiomarkerincriticalneedofstandardization AT josquinmoraly cartcelldetectionscopingreviewanessentialbiomarkerincriticalneedofstandardization |