Bispecific targeting of CD20 and CD19 increases polyfunctionality of chimeric antigen receptor T-cell products in B-cell malignancies. Cytotherapy 2022 Aug;24(8):767-773
Date
05/22/2022Pubmed ID
35597752DOI
10.1016/j.jcyt.2022.03.011Scopus ID
2-s2.0-85130432792 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
BACKGROUND AIMS: Selective immune pressure contributes to relapse due to target antigen downregulation in patients treated with anti-CD19 chimeric antigen receptor (CAR) T cells. Bispecific lentiviral anti-CD20/anti-CD19 (LV20.19) CAR T cells may prevent progression/relapse due to antigen escape. Highly polyfunctional T cells within a CAR T-cell product have been associated with response in single-antigen-targeted anti-CD19 CAR T cells.
METHODS: The authors performed a single-cell proteomic analysis to assess polyfunctional cells in our LV20.19 CAR T-cell product. Analysis was limited to those treated at a fixed dose of 2.5 × 106 cells/kg (n = 16). Unused pre-infusion CAR T cells were thawed, sorted into CD4/CD8 subsets and stimulated with K562 cells transduced to express CD19 or CD20. Single-cell production of 32 individual analytes was measured and polyfunctionality and polyfunctional strength index (PSI) were calculated.
RESULTS: Fifteen patients had adequate leftover cells for analysis upon stimulation with CD19, and nine patients had adequate leftover cells for analysis upon stimulation with CD20. For LV20.19 CAR T cells, PSI was 866-1109 and polyfunctionality was 40-45%, which were higher than previously reported values for other CAR T-cell products.
CONCLUSIONS: Stimulation with either CD19 or CD20 antigens resulted in similar levels of analyte activation, suggesting that this product may have efficacy in CD19- patient populations.
Author List
Zurko JC, Xu H, Chaney K, Schneider D, Szabo A, Hari P, Johnson BD, Shah NNAuthors
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of WisconsinBryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Nirav N. Shah MD Associate Professor in the Medicine department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Data Science Institute department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Antigens, CD19Antigens, CD20
Humans
Immunotherapy, Adoptive
Neoplasm Recurrence, Local
Proteomics
Receptors, Antigen, T-Cell
T-Lymphocytes
