Kinetic characteristics of T cell expansion in patients with B tumor after CAR19 T cell therapy
Objective To investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.Methods Observational study.Flow cytometry was used to monitor the levels of CAR19+and CAR19-T cell expansion and the dynamic changes of T lymphocyte subsets before and after CAR19 T cell therapy.The 52 patients with B-cell hematologic malignancies(including 12 B-ALL and 40 NHL)who received CAR19 T cell therapy in the First Affiliated Hospital of Soochow University from November 2021 to December 2023 were recruited in this study.Patients were divided into complete response group and incomplete response group according to the efficacy evaluation criteria in the treatment guidelines for B-cell hematologic malignancies.T test or non-parametric rank sum test were used to compare the differences of CAR19+and CAR19-T cell subsets between the two groups.Results At the peak of CAR19+T cell expansion,there was no statistic difference of CAR19+T cell subsets between the complete response group and the incomplete response group.After 6 months,the percentage of CD4+T cells(CD3+CD4+CD8-)in CAR19-T cells in patients was lower than the pre-treatment level(48.0+27.2,63.1+19.7,<0.01),and the percentages of CD197+CD45RA+and CD197-CD45RA-subsets recovered to the pre-treatment level,while the percentage of CD197-CD45RA+subset(4.2+3.0,21.1+15.6,<0.01)was lower than the pre-treatment level.The percentage of CD8+T cells(CD3+CD4-CD8+)returned to pre-treatment level after 6 months,CD197-CD45RA-subset in CD8+T cells returned to pre-treatment level,while CD197+CD45RA+subset(16.6+8.7,35.1+30.1,<0.01),CD197+CD45RA-subset(18.7+9.1,25.8+19.1,<0.01)were still lower than pre-treatment level.Conclusion After CAR19 T cell treatment,there was no significant differences in the proportions of CAR19+T cell subsets in patients with different therapeutic effects.After treatment,the proportion of CAR19-CD3+CD4-CD8+cells recovered earlier than CD3+CD4+CD8-cells,and the dynamic changes of each subgroup were different.This therapeutic regimen has a great impact on the subpopulation of CAR19-T cells in vivo,and the reconstruction of such T cells takes a long time.