Effect of PD-1 inhibitor Nivolumab on the proliferation and cytotoxicity of anti-CD19 chimeric antigen receptor T cells.
10.3760/cma.j.issn.0253-2727.2018.07.011
- Author:
Hai Bo ZHU
1
;
Qi DENG
;
Rui ZHANG
;
Yan Yu JIANG
;
Juan Xia MENG
;
Ming Feng ZHAO
;
Yu Ming LI
;
Rui CUI
Author Information
1. Department of Hematology, Tianjin First Central Hospital, Tianjin 300192, China.
- Publication Type:Journal Article
- Keywords:
Chimeric antigen receptor;
Lymphoma;
PD-1 inhibitor
- MeSH:
Antigens, CD19;
Cell Proliferation;
Humans;
Leukocytes, Mononuclear;
Nivolumab/pharmacology*;
Programmed Cell Death 1 Receptor;
Receptors, Antigen, T-Cell;
Receptors, Chimeric Antigen;
T-Lymphocytes
- From:
Chinese Journal of Hematology
2018;39(7):584-588
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To Evaluation the effect of PD-1 inhibitor Nivolumab on the proliferation and cytotoxicity of anti-CD19 chimeric antigen receptor T cells (CD19-CAR-T) in vitro. Methods: Five patients with high PD-1 expression in peripheral blood and five healthy volunteers were selected. These peripheral blood mononuclear cells were used as the source of T cells to prepare CD19-CAR-T cells. Different doses (72, 36, 18 μg/ml) of Nivolumab was added on day 8 to the culture medium. Patient T cells incubated with 72 μg/ml Nivolumab and CD19-CAR-T cells of healthy volunteers were used as controls. CCK-8, lactate dehydrogenase (LDH) cytotoxicity assay and ELASA were used to detect the proliferation capacity, the specific cytotoxicity and the inflammatory factor secretion. Results: ①T cells from patients with high expression of PD-1 as the source of CD19-CAR-T cells did not affect transfection rate compared with that of healthy volunteers [(32.80±7.22)% vs (35.10±5.84)%, t=-0.554, P=0.593]. ②Incubation of CD19-CAR-T cells with 72 μg/ml Nivolumab did not affect CD19-CAR-T cell proliferation, but its cytotoxicity was significantly higher than that of CD19-CAR-T cells alone or patients' T cells +72 μg/ml Nivolumab (all P<0.001), there was no significant difference in the killing activity between the 72 μg/ml and 36 μg/ml Nivolumab treated CD19-CAR-T cells on Pfeiffer cells (P=0.281, 0.267, respectively), and they were all higher than those of 18 μg/ml Nivolumab treated CD19-CAR-T cells (all P<0.001). ③Different doses of PD-1 inhibitor Nivolumab combined with CD19-CAR-T cells does not affect the secretion of IFN-γ and IFN-α (all P>0.05). Conclusion: Combination of 36 μg/ml PD-1 inhibitor and CD19-CAR-T cells could reduce the drug toxicity and enhance the cytotoxicity.
