BACH2 is a putative T-cell lymphoma tumor suppressor that may play a role in product-derived CAR T-cell lymphomas
| العنوان: | BACH2 is a putative T-cell lymphoma tumor suppressor that may play a role in product-derived CAR T-cell lymphomas |
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| المؤلفون: | Jay Daniels, Jaehyuk Choi |
| المصدر: | Blood |
| بيانات النشر: | American Society of Hematology, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Lymphoma, Antigens, CD19, Immunology, Plenary Paper, Cell Biology, Hematology, Biology, Lymphoma, T-Cell, medicine.disease, Biochemistry, law.invention, Basic-Leucine Zipper Transcription Factors, law, Product (mathematics), Cancer research, medicine, Humans, Suppressor, T-cell lymphoma, Car t cells, Letter to Blood |
| الوصف: | We performed a phase 1 clinical trial to evaluate outcomes in patients receiving donor-derived CD19-specific chimeric antigen receptor (CAR) T cells for B-cell malignancy that relapsed or persisted after matched related allogeneic hemopoietic stem cell transplant. To overcome the cost and transgene-capacity limitations of traditional viral vectors, CAR T cells were produced using the piggyBac transposon system of genetic modification. Following CAR T-cell infusion, 1 patient developed a gradually enlarging retroperitoneal tumor due to a CAR-expressing CD4(+) T-cell lymphoma. Screening of other patients led to the detection, in an asymptomatic patient, of a second CAR T-cell tumor in thoracic para-aortic lymph nodes. Analysis of the first lymphoma showed a high transgene copy number, but no insertion into typical oncogenes. There were also structural changes such as altered genomic copy number and point mutations unrelated to the insertion sites. Transcriptome analysis showed transgene promoter–driven upregulation of transcription of surrounding regions despite insulator sequences surrounding the transgene. However, marked global changes in transcription predominantly correlated with gene copy number rather than insertion sites. In both patients, the CAR T-cell–derived lymphoma progressed and 1 patient died. We describe the first 2 cases of malignant lymphoma derived from CAR gene–modified T cells. Although CAR T cells have an enviable record of safety to date, our results emphasize the need for caution and regular follow-up of CAR T recipients, especially when novel methods of gene transfer are used to create genetically modified immune therapies. This trial was registered at www.anzctr.org.au as ACTRN12617001579381. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::039e057689f569ada9b78b6b3b7acaf3 https://doi.org/10.1182/blood.2021012641 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....039e057689f569ada9b78b6b3b7acaf3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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