The prognosis of patients with large B-cell lymphoma (LBCL) that progresses after treatment with chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CAR19) is poor. We report on the first 3 consecutive patients with autologous CAR19-refractory LBCL who were treated with a single infusion of autologous 1 × 106 CAR+ T cells per kilogram targeting CD22 (CAR22) as part of a phase 1 dose-escalation study. CAR22 therapy was relatively well tolerated, without any observed nonhematologic adverse events higher than grade 2. After infusion, all 3 patients achieved complete remission, with all responses continuing at the time of last follow-up (mean, 7.8 months; range, 6-9.3). Circulating CAR22 cells demonstrated robust expansion (peak range, 85.4-350 cells per microliter), and persisted beyond 3 months in all patients with continued radiographic responses and corresponding decreases in circulating tumor DNA beyond 6 months after infusion. Further accrual at a higher dose level in this phase 1 dose-escalation study is ongoing and will explore the role of this therapy in patients in whom prior CAR T-cell therapies have failed. This trial is registered on clinicaltrials.gov as #NCT04088890.
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:
The efficacy and safety of chimeric antigen receptor (CAR) T cell therapy is still inconclusive in solid tumor treatment. Recently, nanotechnology has emerged as a potent strategy to reshape CAR-T cell therapy with promising outcomes. This review aims to discuss the significant potential of nano-engineered CAR-T cell therapy in addressing existing challenges, including CAR-T cell engineering evolution, tumor microenvironment (TME) modulation, and precise CAR-T cell therapy (precise targeting, monitoring, and activation), under the main consideration of clinical translation.
Introduction: Approximately one-third of all AML patients have a mutation in the Fms-like tyrosine kinase 3 () gene, which is associated with a poor prognosis in these individuals. The 2017 approval of midostaurin, the first FLT3 inhibitor, spurred extensive development of more potent and selective inhibitors with an improved safety profile.
Areas Covered: This review analyzes patent inventions for the treatment of AML using FLT3 inhibitors, covering developments from the earliest to the most recent, disclosed in 2024.
This study explores a novel therapeutic strategy for relapsed/refractory (R/R) Burkitt lymphoma (BL) by integrating autologous hematopoietic stem cell transplantation (ASCT) with tandem anti-CD19/CD22 chimeric antigen receptor (CAR) T cell therapy. A 20-year-old Asian male with refractory BL, whose lymphoma had not responded to multiple chemoimmunotherapy regimens, received myeloablative ASCT followed three days later by infusion of a novel third-generation CAR T cells engineered with CD28 and CD3ζ signaling domains, along with a TLR2 costimulatory domain. This resulted in sustained complete remission at the 306-day follow-up, without experiencing any severe complications.
The risk of cytokine release syndrome (CRS) in patients with infections prior to chimeric antigen receptor T-cell (CAR T-cell) therapy represents an important and underreported event. Patients with active infections needing prompt CAR T-cell therapy to treat aggressive hematologic malignancies remain a clinical challenge. This case describes the clinical course of a 35-year-old male patient with relapsed/refractory T-cell/histiocyte-rich large B-cell lymphoma who received axicabtagene ciloleucel.
