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Chimeric antigen receptor T cells for sustained remissions in leukemia.
Chimeric antigen receptor-modified T-cell therapy against CD19 was effective in treating relapsed and refractory ALL and was associated with a high remission rate, even among patients for whom stem-cell transplantation had failed, and durable remissions up to 24 months were observed. Expand
Tisagenlecleucel in Children and Young Adults with B‐Cell Lymphoblastic Leukemia
- S. Maude, T. Laetsch, +32 authors S. Grupp
- The New England journal of medicine
- 31 January 2018
In this global study of CAR T‐cell therapy, a single infusion of tisagenlecleucel provided durable remission with long‐term persistence in pediatric and young adult patients with relapsed or refractory B‐cell ALL, with transient high‐grade toxic effects. Expand
Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia.
Several genetic alterations that activate kinase signaling in Ph-like ALL induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy. Expand
Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia.
The first models that can accurately predict which patients are likely to develop severe CRS before they become critically ill are developed, which improves understanding of CRS biology and may guide future cytokine-directed therapy. Expand
CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia.
The current landscape of CD19 CAR clinical trials, CRS pathophysiology and management, and remaining challenges are discussed, including the importance of duration of remission and CAR-modified T-cell persistence. Expand
Managing Cytokine Release Syndrome Associated With Novel T Cell-Engaging Therapies
One approach has developed targets IL-6, a prominent cytokine in CRS, using the IL- 6R antagonist tocilizumab, which has the potential to provide superior toxicity control without compromising efficacy. Expand
Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy.
- E. Sotillo, D. Barrett, +27 authors A. Thomas-Tikhonenko
- Biology, Medicine
- Cancer discovery
- 1 December 2015
It is discovered that the underlying mechanism is the selection for preexisting alternatively spliced CD19 isoforms with the compromised CART-19 epitope, which suggests a possibility of targeting alternative CD19 ectodomains, which could improve survival of patients with B-cell neoplasms. Expand
Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia
Clinicians should be aware of expanding use of this breakthrough therapy and implications for critical care units in cancer centers and the timing, severity, and intensive care management of cytokine release syndrome after chimeric antigen receptor–modified T cell therapy. Expand
Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy.
Patients treated with T cell-activating therapies, including blinatumomab, should be monitored for HLH, and cytokine-directed therapy may be considered in cases of life-threatening CRS. Expand
Durable Remissions in Children with Relapsed/Refractory ALL Treated with T Cells Engineered with a CD19-Targeted Chimeric Antigen Receptor (CTL019)
CTL019 cells can undergo robust in vivo expansion and can persist for 3 years or longer in children and young adults with r/r ALL, allowing for the possibility of long-term disease control without subsequent therapy such as SCT. Expand