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Updated: Mar 20, 2026

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells

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Published on: August 1, 2025

In vivo site-specific engineering to reprogram T cells.

William A Nyberg^1,2,3,4, Pierre-Louis Bernard^1,2, Wayne Ngo^5,6,7

¹Department of Medicine, Division of Hematology-Oncology, University of California, San Francisco, San Francisco, CA, USA.

|March 19, 2026

Summary

This summary is machine-generated.

Researchers developed a novel in vivo method for generating chimeric antigen receptor (CAR) T cells. This site-specific gene integration technique offers a more efficient and accessible pathway for advanced T cell therapies.

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Published on: November 11, 2016

Area of Science:

Immunology
Gene Therapy
Cancer Research

Background:

Engineered T cells (CAR-T, TCR-T) show promise for cancer, autoimmune, and infectious diseases.
Genome editing enhances T cell function but ex vivo manufacturing is costly and time-consuming.
In vivo generation of CAR-T cells is desirable but faces challenges with transient expression or random integration.

Purpose of the Study:

To develop a method for stable, cell-specific transgene expression via in vivo site-specific integration of large DNA payloads.
To overcome the limitations of ex vivo T cell manufacturing and current in vivo approaches.

Main Methods:

A two-vector system was developed using CRISPR-Cas9 ribonucleoproteins and a DNA donor template.
Enveloped delivery vehicles and adeno-associated viruses were optimized for T cell-specific delivery.
CAR transgene was integrated into a T cell-specific locus in humanized mouse models.

Main Results:

Stable and cell-specific transgene expression was achieved in vivo.
Therapeutic levels of CAR T cells were generated in vivo in models of B cell aplasia, hematological, and solid malignancies.
The method demonstrated efficient T cell-specific delivery and gene-targeting.

Conclusions:

In vivo site-specific integration enables precise and stable CAR T cell generation.
This approach offers a more efficient, precise, and accessible alternative to ex vivo manufacturing.
The findings pave the way for broader application of T cell-based therapies.