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Published on: February 27, 2019
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Optimizing In Vivo CAR T-cell Engineering for Cancer Immunotherapy
Ruiheng Wang1,2, Jianhua Yu3,4,5, Michael A Caligiuri1,2,6
1Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, California.
Cancer Research
|January 6, 2026
Summary
In vivo chimeric antigen receptor (CAR)-T cell therapy engineers T cells inside the body, overcoming limitations of traditional ex vivo methods. This review explores novel delivery systems for enhanced CAR-T cell therapy accessibility and efficacy.
Area of Science:
- Immunology
- Biotechnology
- Gene Therapy
Background:
- Chimeric antigen receptor (CAR)-T cell therapy shows promise for hematologic malignancies but faces manufacturing challenges.
- Conventional ex vivo CAR-T production is costly, complex, and limits scalability and accessibility.
Purpose of the Study:
- To review current in vivo CAR-T cell engineering strategies and delivery systems.
- To discuss advancements in achieving efficient, specific, and safe CAR transgene transfer.
- To explore challenges and future directions for in vivo CAR-T therapy.
Main Methods:
- Review of viral vectors (lentiviruses, retroviruses, AAVs, viral-like particles) for in vivo CAR-T delivery.
- Analysis of non-viral systems including lipid nanoparticles and polymer-based carriers.
- Examination of vector tropism, membrane modifications, and targeting ligand design principles.
Main Results:
- In vivo CAR-T engineering bypasses ex vivo manipulation, offering a potentially more accessible therapeutic approach.
- Various viral and non-viral delivery platforms are being engineered for targeted CAR transgene expression.
- Preclinical and clinical studies are evaluating the safety and efficacy of these in vivo strategies.
Conclusions:
- In vivo CAR-T cell engineering presents a transformative alternative to ex vivo manufacturing.
- Optimizing vector stability, T cell targeting, and reducing immunogenicity are key for clinical advancement.
- Further development is crucial to broaden the clinical application of in vivo CAR-T therapies.
