Publications by authors named "S Libertini"
The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. The PTCL had a clonal T-cell receptor rearrangement, which was already detectable in the apheresis product for CAR T-cell manufacturing and 7 months earlier for autologous transplantation. Somatic and mutations in CD34+ stem cells and their progeny were detected in the PTCL, in the apheresis specimen that was obtained for CAR T-cell production, and in the autotransplant.
View Article and Find Full Text PDFAt the 8th International Workshop on Genotoxicity Testing meeting in Ottawa, in August 2022, a plenary session was dedicated to the genotoxicity risk evaluation of gene therapies, including insertional oncogenesis and off-target genome editing. This brief communication summarizes the topics of discussion and the main insights from the speakers. Common themes included recommendations to conduct tailored risk assessments based on a weight-of-evidence approach, to promote data sharing, transparency, and cooperation between stakeholders, and to develop state-of-the-art validated tests relevant to clinical scenarios.
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- - The study focused on the safety concerns of residual undifferentiated pluripotent stem cells (PSCs) in cell therapy products (CTPs), which could lead to tumor formation in clinical applications.
- - Researchers tested a droplet digital PCR (ddPCR) method to detect leftover induced pluripotent stem cells (iPSCs) in cardiomyocyte samples by varying their concentrations and measuring specific iPSC markers for accuracy.
- - Findings indicated that the RT-ddPCR assay effectively identifies iPSC impurities in CTPs, with variability primarily arising from how iPSCs were added to samples, showcasing the method's potential for ensuring safety in PSC-derived therapies.
Article Synopsis
- Regulators and industry experts are looking for better ways to assess the cancer-causing potential of gene therapies, as current methods may not be sufficient.
- A meeting in London in March 2023 brought together specialists to reach a consensus on key themes such as vector genotoxicity, uncertainty sources, and appropriate toxicological endpoints for gene therapy evaluation.
- The recommendations from this meeting aim to guide the creation of new regulatory guidelines for the nonclinical toxicological assessment of gene therapy products.
Spinal muscular atrophy is an autosomal recessive disease resulting in motor neuron degeneration and progressive life-limiting motor deficits when untreated. Onasemnogene abeparvovec is an adeno-associated virus serotype 9-based gene therapy that improves survival, motor function, and motor milestone achievement in symptomatic and presymptomatic patients. Although the adeno-associated virus genome is maintained as an episome, theoretical risk of tumorigenicity persists should genomic insertion occur.
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