Authors
Victoria Duback, Shalu S Kharkwal, Vasily Vagin, Kerrie Paterson, Alicia Sabbio, Joohwan Kim, Amey Gaikwad, Jesse Green, Brian Dolinski, Kelan Hlavaty, Garrett Zipp, Shannon Joyce, Abigail Koppes, Bindu Varghese, Kyle Trudeau, Jagesh Shah, Terry Fry, Kutlu G Elpek
Published in
Molecular therapy. Advances. Volume 34. Issue 3. Pages 201803. Sep 10, 2026. Epub Jul 03, 2026.
Abstract
Given challenges with access, manufacturability, and the requirement for lymphodepletion with autologous chimeric antigen receptor (CAR)-T cell therapy, a promising alternative is in vivo-mediated gene delivery using redirected viral vectors to generate tumor-antigen-specific CAR-T cells. While data supporting in vivo CAR-T cells in patients are emerging, limited studies have described the pharmacokinetics (PK) and pharmacodynamics (PD) of this approach. Here, we evaluated the PK/PD of a novel CD8-targeted lentiviral vector called "fusosome," delivering a CD19-directed CAR transgene in xenograft mouse models. In NSG mice without target cells, the fusosome vector genomes cleared rapidly from plasma (90 minutes to 2 hours) and were detectable in tested tissues for up to 1 week. We observed prolonged persistence of viral particles in peripheral blood mononuclear cell (PBMC)-engrafted mice, with vector detection peaking within 10-40 min post-administration, depending on the tissue type. CAR transgene was detectable in various lymphoid organs after 7 days post-vector dosing. Dose-dependent tumor control and specific CAR-T cell generation were observed in tumor-bearing PBMC-engrafted mice. Overall, the PK/PD of fusosome and efficacy in the tumor model supports its potential as an in vivo gene delivery approach to treat patients with B cell lymphomas.
PMID:
42502508
Bibliographic data and abstract were imported from PubMed on 26 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 4
- Comments 0