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Updated: May 22, 2026

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
In vivo CAR-cell therapy: current challenges and emerging therapeutic advances.
Yi-Min Yang1,2, Bo Bao1,2, Yu-Hao Cao1,2
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #169, Xi'an, 710032, China.
In vivo chimeric antigen receptor (CAR) cell therapy is shifting to in situ editing for better accessibility. This review explores delivery methods, challenges like precision and persistence, and future directions for safer, more effective CAR therapies.
Area of Science:
- Immunology
- Biotechnology
- Gene Therapy
Background:
- Chimeric antigen receptor (CAR) cell therapy is transitioning from ex vivo manufacturing to in situ cellular editing for improved therapeutic accessibility.
- Advances in viral and non-viral delivery platforms and CAR-T, CAR-NK, and CAR-M cell types show promise, but face challenges in delivery precision, cellular persistence, and safety.
Purpose of the Study:
- To systematically review current in vivo gene transfer delivery platforms for CAR cell therapy.
- To compare CAR-T, CAR-NK, and CAR-M strategies in overcoming tumor-specific barriers.
- To highlight emerging technologies and future directions for next-generation in vivo CAR therapies.
Main Methods:
- Systematic examination of viral (lentiviral, AAV) and non-viral (lipid nanoparticle) delivery mechanisms.
- Comparative analysis of CAR-T, CAR-NK, and CAR-M platform strategies against tumor heterogeneity and microenvironment barriers.
- Review of emerging frontiers including AI-guided design, smart delivery systems, and synthetic immune systems.
Main Results:
- Current delivery platforms face limitations in precision, persistence, TME resistance, and safety controllability.
- CAR-T, CAR-NK, and CAR-M platforms offer distinct approaches to address tumor complexities.
- Emerging technologies promise enhanced personalization, control, and efficacy.
Conclusions:
- Significant translational bottlenecks remain in in vivo CAR cell therapy despite platform advancements.
- Multidisciplinary approaches integrating AI and novel delivery systems are crucial for future development.
- This review provides a roadmap for advancing safe, precise, and effective in vivo CAR therapies.
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