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Related Experiment Video

Updated: Jun 28, 2025

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
06:10

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates

Published on: May 9, 2025

195

Direct in vivo CAR T cell engineering.

Lauralie Short1, Robert A Holt2, Pieter R Cullis3

  • 1Michael Smith Genome Sciences Department, BC Cancer Research Institute, Vancouver, BC, Canada; Interdisciplinary Oncology Program, University of British Columbia, Vancouver, BC, Canada.

Trends in Pharmacological Sciences
|April 13, 2024
PubMed
Summary

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GPNMB-directed CAR T cell therapy against MiT/TFE-family fusion-driven solid tumors.

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Chimeric antigen receptor (CAR) T-cell therapy shows promise for blood cancers. In vivo generation of CAR T cells offers a potentially simpler and more cost-effective alternative to ex vivo manufacturing, with ongoing research addressing clinical challenges.

Area of Science:

  • Immunotherapy
  • Cellular Therapy
  • Oncology

Background:

  • Chimeric antigen receptor (CAR) T-cell therapy is a powerful treatment for relapsed/refractory blood cancers.
  • Current ex vivo manufacturing is complex and costly, limiting widespread adoption.
  • In vivo generation of CAR T cells is an emerging alternative strategy.

Purpose of the Study:

  • To review the ex vivo CAR T-cell manufacturing process.
  • To explore in vivo CAR T-cell generation strategies.
  • To discuss the potential and challenges of in vivo CAR T-cell therapy.

Main Methods:

  • Review of ex vivo manufacturing processes.
  • Analysis of preclinical data for in vivo CAR T-cell generation.
  • Discussion of delivery methods, including nanoparticle-formulated nucleic acids and viral vectors.
Keywords:
DNAchimeric antigen receptorengineered lentivirusesin vivo cell therapylipid nanoparticlesmRNApolymer nanoparticles

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Main Results:

  • In vivo strategies aim to simplify CAR T-cell production, reducing complexity and cost.
  • Preclinical models demonstrate the potency of in vivo generated CAR T cells.
  • Potential applications extend beyond current indications for CAR T-cell therapy.

Conclusions:

  • In vivo CAR T-cell generation presents a promising, potentially more accessible therapeutic approach.
  • Further research is needed to address challenges in delivery specificity, long-term efficacy, and safety for clinical readiness.
  • This approach could broaden the impact of CAR T-cell therapy in various diseases.