Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) constitutes a heterogeneous subset of ALL with a uniformly unfavorable prognosis. The identification of mutations amenable to treatment with tyrosine kinase-inhibitors (TKIs) represents a promising field of investigation. We report the case of a young patient affected by relapsed/refractory Ph-like ALL treated with chimeric antigen receptor T (CAR-T) cells after successful bridging with compassionate-use ponatinib and low-dose prednisone. We restarted low-dose ponatinib maintenance three months later. Twenty months later, measurable residual disease negativity and B-cell aplasia persist. To the best of our knowledge, this is the first case reporting the use of ponatinib in Ph-like ALL as a bridge to and maintenance after CAR-T cell therapy.
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http://dx.doi.org/10.3389/fonc.2022.1100105 | DOI Listing |
Front Immunol
December 2024
Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.
Introduction: Challenges remain in reducing antigen escape and tumor recurrence while CAR-T cell therapy has substantially improved outcomes in the treatment of multiple myeloma. T cell receptor fusion construct (TRuC)-T cells, which utilize intact T cell receptor (TCR)-CD3 complex to eliminate tumor cells in a non-major histocompatibility complex (MHC)-restricted manner, represent a promising strategy. Moreover, interleukin-7 (IL-7) is known to enhance the proliferation and survival of T cells.
View Article and Find Full Text PDFFront Immunol
December 2024
Tumor Vaccine and Biotechnology Branch, Office of Cellular Therapy and Human Tissues, Office of Therapeutic Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration (U.S. FDA), Silver Spring, MD, United States.
Introduction: CAR-T cell therapy is associated with life-threatening inflammatory toxicities, partly due to the activation and secretion of inflammatory cytokines by bystander myeloid cells (BMCs). However, due to limited clinical data, it is unclear whether CAR-NK cells cause similar toxicities.
Methods: We characterized the soluble factors (SFs) released by activated human CAR-T and CAR-NK cells and assessed their role in BMC activation (BMCA).
Curr Hematol Malig Rep
January 2025
Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Purpose Of Review: More than a decade following the discovery of Calreticulin (CALR) mutations as drivers of myeloproliferative neoplasms (MPN), advances in the understanding of CALR-mutant MPN continue to emerge. Here, we summarize recent advances in mehanistic understanding and in targeted therapies for CALR-mutant MPN.
Recent Findings: Structural insights revealed that the mutant CALR-MPL complex is a tetramer and the mutant CALR C-terminus is exposed on the cell surface.
Cancer Discov
January 2025
Stanford University, Stanford, California, United States.
Patients with large B-cell lymphoma (LBCL) progressing after anti-CD19 CAR T-cell (CAR19) therapy have poor outcomes. Subsequent CAR T-cell therapy shows promise, but the impact of residual CAR19 and early relapse remains unclear. We evaluated 37 CAR19-refractory LBCL patients who received anti-CD22 CAR T-cell (CAR22) in a phase 1b trial (NCT04088890).
View Article and Find Full Text PDFNat Med
January 2025
Seattle Children's Therapeutics, Seattle, WA, USA.
Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG.
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