Synergistic effect of ibrutinib and CD19 CAR‐T cells on Raji cells in vivo and in vitro
| العنوان: | Synergistic effect of ibrutinib and CD19 CAR‐T cells on Raji cells in vivo and in vitro |
|---|---|
| المؤلفون: | Yanyu Jiang, Q Deng, Rui Zhang, Lei Sun, Juan Mu, Meijing Liu, Zheng Li, Xuelin Wang |
| المصدر: | Cancer Science |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cancer Research, programmed cell death‐ligand 1, T-Lymphocytes, Chronic lymphocytic leukemia, Cell, Immunotherapy, Adoptive, Mice, chemistry.chemical_compound, Basic and Clinical Immunology, Raji cell line, 0302 clinical medicine, Piperidines, hemic and lymphatic diseases, chimeric antigen receptor, medicine.diagnostic_test, biology, Chemistry, General Medicine, Middle Aged, Combined Modality Therapy, Raji cell, Treatment Outcome, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Ibrutinib, Original Article, Female, Lymphoma, Large B-Cell, Diffuse, Adult, STAT3 Transcription Factor, Antigens, CD19, Receptors, Antigen, T-Cell, Bruton tyrosine kinase inhibitor, CD19, Immunophenotyping, Flow cytometry, 03 medical and health sciences, In vivo, Cell Line, Tumor, Biomarkers, Tumor, medicine, tumor microenvironment, Animals, Humans, Protein Kinase Inhibitors, Aged, Neoplasm Staging, Tumor microenvironment, Adenine, Original Articles, medicine.disease, Xenograft Model Antitumor Assays, Disease Models, Animal, 030104 developmental biology, biology.protein, Cancer research |
| الوصف: | Ibrutinib might improve the efficacy of anti‐CD19 chimeric antigen receptor (CD19 CAR) T‐cell therapy in chronic lymphocytic leukemia (CLL). We studied the possibility and mechanism of the synergistic effect of ibrutinib and CAR‐T cells in other types of lymphoma. In this study, we selected the CD19 CAR‐T cells of a patient with lymphoma who failed in his CD19 CAR‐T‐cell therapy and a dose of 8 mg/kg/d ibrutinib. Subcutaneous and tail vein tumorigenic mice were established with Raji cells. The differences in the synergistic effect between these 2 models were compared by bioluminescence imaging (BLI) monitoring and flow cytometry (FCM). The expression of the STAT‐3 signaling pathway was assessed by western blot analysis. There was no synergistic effect of ibrutinib and CD19 CAR‐T cells in vitro. Programmed cell death‐ligand 1 (PD‐L1) was expressed in 0.23 ± 0.06% of Raji cells. In the subcutaneous tumorigenic model, the luciferase signal was reduced significantly in the group receiving ibrutinib combined with CD19 CAR‐T cells. Moreover, the proportion of CD19 CAR‐T cells was higher in the polytherapy group than in the CAR‐T‐cell monotherapy group. However, we did not get an analogous synergistic effect in the tail vein tumorigenic model. STAT‐3 signaling pathway expression in the residual tumor cells did not differ between those with and those without ibrutinib, suggesting that the IL‐10/STAT‐3/PD‐L1 pathway was not involved in the synergistic effect. Therefore, some other mechanism might be a target for ibrutinib. Our results provide evidence for the use of ibrutinib in polytherapy for other types of B‐cell lymphoma. Our results might indicate that no IL‐10/STAT‐3/PD‐L1 pathways were involved in the synergistic effect. Then some other mechanism in the microenvironment might be a possible target for ibrutinib. We expect our results would provide evidence for the use of ibrutinib in polytherapy for other types of B‐cell lymphoma. |
| تدمد: | 1349-7006 1347-9032 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f49d2425f68eed7413004c23fbb5d00bTest https://doi.org/10.1111/cas.14638Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f49d2425f68eed7413004c23fbb5d00b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
|---|