91P Identification of T cell receptors from tumour-infiltrating lymphocytes cross-reactive to multiple patient-derived metastatic melanoma cell lines using CRISPR-cas9 mediated TCR replacement
PTPRZ1-specific TCR-T cells (TCT-001), administered via a catheter placed during reresection, with or without preceding lymphodepletion.Biomarker studies include advanced MRI and longitudinal immune profiling of blood and cerebrospinal fluid.For engineering patient autologous T cells, we developed a customized non-viral nSMAR DNA vector-based manufacturing process on the CliniMACS Prodigy platform.Results: Benchmarking of our customized manufacturing pipeline confirmed feasibility, reproducibility, and scalability in GMP-compliant settings.Cell engineering consistency of >45% was achieved through electroporation with recovery rates >80%.The cryopreserved product demonstrated optimal post-thaw viability, with validation confirming retained cytotoxic potency.Conclusions: INVENT4GB establishes a first-in-human clinical evaluation of PTPRZ1specific TCR-T in GB.Beyond assessing safety and early efficacy, this trial provides proof-of-concept for a faster, cost-efficient, and clinically translatable non-viral strategy for producing T cell therapies, potentially broadening accessibility and accelerating future development.
Authors
- L. Schuster
- M.D.D. Crowther
- S.A. Tvingsholm
- K.H. Johansen
- Ö. Met
- M.C.W. Westergaard
- I.M. Svane
- S. Reker Hadrup
Institutions
- Herlev Hospital (DK)
- Gentofte Hospital (DK)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Immuno-Oncology Technology
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1016/j.iotech.2025.101176
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00