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From bench to body: In vivo CAR engineering in the clinic

Yan-Ruide Li1, Lili Yang2

  • 1Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Cell Reports. Medicine
|November 19, 2025
PubMed

Insights

In vivo CAR engineering shows promise for treating cancer and autoimmune diseases. Advanced delivery systems are enabling clinical trials, demonstrating initial safety and efficacy, though challenges remain.

Area of Science:

  • Immunotherapy
  • Gene Therapy
  • Oncology

Background:

  • Chimeric antigen receptor (CAR) T-cell therapy has revolutionized cancer treatment.
  • In vivo CAR engineering offers a novel approach to CAR T-cell therapy, aiming to engineer T-cells directly within the body.
  • This strategy holds potential for treating both cancer and autoimmune diseases.

Purpose of the Study:

  • To critically discuss the opportunities and translational hurdles of in vivo CAR engineering.
  • To highlight the advancements in delivery systems enabling this therapeutic platform.
  • To provide an overview of the current clinical progress.

Main Methods:

  • Review of current literature and clinical trial data on in vivo CAR engineering.
  • Analysis of advanced delivery systems, including immune-evasive lentiviral vectors and targeted lipid nanoparticles.
  • Discussion of key challenges in translating this technology to widespread clinical use.

Main Results:

  • In vivo CAR engineering has progressed to early clinical testing.
  • Initial clinical studies have demonstrated promising safety and efficacy profiles.
  • Advanced delivery systems are crucial for the success of this approach.

Conclusions:

  • In vivo CAR engineering is a rapidly advancing therapeutic platform with significant potential.
  • Overcoming translational hurdles is essential for broader clinical application.
  • Continued research and development in delivery systems will drive future progress.

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