Language:

CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients

The Journal of clinical investigation, 2016-06, Vol.126 (6), p.2123-2138 [Peer Reviewed Journal]

Copyright © 2016, American Society for Clinical Investigation 2016 American Society for Clinical Investigation ;ISSN: 0021-9738 ;EISSN: 1558-8238 ;DOI: 10.1172/JCI85309 ;PMID: 27111235

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients
Author: Turtle, Cameron J ; Hanafi, Laïla-Aïcha ; Berger, Carolina ; Gooley, Theodore A ; Cherian, Sindhu ; Hudecek, Michael ; Sommermeyer, Daniel ; Melville, Katherine ; Pender, Barbara ; Budiarto, Tanya M ; Robinson, Emily ; Steevens, Natalia N ; Chaney, Colette ; Soma, Lorinda ; Chen, Xueyan ; Yeung, Cecilia ; Wood, Brent ; Li, Daniel ; Cao, Jianhong ; Heimfeld, Shelly ; Jensen, Michael C ; Riddell, Stanley R ; Maloney, David G
Subjects: Adult ; Aged ; CD4-CD8 Ratio ; Clinical Medicine ; Disease-Free Survival ; Humans ; Immunotherapy, Adoptive - adverse effects ; Immunotherapy, Adoptive - methods ; Lymphocyte Depletion - methods ; Middle Aged ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy ; Receptors, Antigen, T-Cell - immunology ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - transplantation ; Tumor Burden - immunology ; Young Adult
Is Part Of: The Journal of clinical investigation, 2016-06, Vol.126 (6), p.2123-2138
Description: T cells that have been modified to express a CD19-specific chimeric antigen receptor (CAR) have antitumor activity in B cell malignancies; however, identification of the factors that determine toxicity and efficacy of these T cells has been challenging in prior studies in which phenotypically heterogeneous CAR-T cell products were prepared from unselected T cells. We conducted a clinical trial to evaluate CD19 CAR-T cells that were manufactured from defined CD4+ and CD8+ T cell subsets and administered in a defined CD4+:CD8+ composition to adults with B cell acute lymphoblastic leukemia after lymphodepletion chemotherapy. The defined composition product was remarkably potent, as 27 of 29 patients (93%) achieved BM remission, as determined by flow cytometry. We established that high CAR-T cell doses and tumor burden increase the risks of severe cytokine release syndrome and neurotoxicity. Moreover, we identified serum biomarkers that allow testing of early intervention strategies in patients at the highest risk of toxicity. Risk-stratified CAR-T cell dosing based on BM disease burden decreased toxicity. CD8+ T cell-mediated anti-CAR transgene product immune responses developed after CAR-T cell infusion in some patients, limited CAR-T cell persistence, and increased relapse risk. Addition of fludarabine to the lymphodepletion regimen improved CAR-T cell persistence and disease-free survival. Immunotherapy with a CAR-T cell product of defined composition enabled identification of factors that correlated with CAR-T cell expansion, persistence, and toxicity and facilitated design of lymphodepletion and CAR-T cell dosing strategies that mitigated toxicity and improved disease-free survival. ClinicalTrials.gov NCT01865617. R01-CA136551; Life Science Development Fund; Juno Therapeutics; Bezos Family Foundation.
Publisher: United States: American Society for Clinical Investigation
Language: English
Identifier: ISSN: 0021-9738
EISSN: 1558-8238
DOI: 10.1172/JCI85309
PMID: 27111235
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
ProQuest Central

Back to results list

Previous Result 18 Next Go to Next page


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients

Copyright © 2016, American Society for Clinical Investigation 2016 American Society for Clinical Investigation ;ISSN: 0021-9738 ;EISSN: 1558-8238 ;DOI: 10.1172/JCI85309 ;PMID: 27111235

Searching Remote Databases, Please Wait