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In Vivo CAR-T Cell Engineering: Translating Vector Pharmacology into Therapeutic Performance

  • Jiaqiang Ren *,   
  • David Stroncek,   
  • Anh Dinh

Received: 11 Jun 2026 | Revised: 27 Aug 2026 | Accepted: 02 Sep 2026 | Published: 10 Sep 2026

Abstract

In Vivo CAR-T cell engineering delivers chimeric antigen receptor (CAR) molecules transgenes directly to endogenous T cells using lentiviral vectors or targeted lipid nanoparticles, bypassing the manufacturing processes of ex vivo cellular therapies. Lentiviral vectors provide integration-based expression for sustained tumor control, whereas lipid nanoparticles enable transient, repeat-dosable therapies for autoimmune disease. First-in-human clinical trials have confirmed proof-of-concept: CAR-T cells expand, deplete target cells, and generate clinical responses, including negative minimal residual disease in multiple myeloma and induce B-cell depletion in systemic lupus erythematosus. However, persistence remains substantially shorter than ex vivo CAR T cell products. This review presents platform architecture, preclinical data, and emerging clinical evidence. We propose a Quality-by-Design (QbD) framework-a systematic, science- and risk-based development approach that begins with predefined product objectives and links critical quality attributes to material attributes and process controls- integrating vector pharmacology with immune parameters and discuss development pathways that emphasize platform–indication matching, innate immune evasion, and adjunctive T-cell conditioning to address the persistence gap and safety control.

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Ren, J.; Stroncek, D.; Dinh, A. In Vivo CAR-T Cell Engineering: Translating Vector Pharmacology into Therapeutic Performance. Translational Insights 2026, 1 (1), 19. https://doi.org/10.53941/ti.2026.100019.
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