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Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
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Published on: May 9, 2025

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Genetic engineering strategies to enhance antitumor reactivity and reduce alloreactivity for allogeneic cell-based

Yuning Chen1, Yichen Zhu1, Adam Kramer1

  • 1Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States.

Frontiers in Medicine
|April 17, 2023
PubMed

Insights

Genetic engineering of CAR-T cells offers potential for universal cancer immunotherapy. Strategies are being developed to overcome graft-versus-host disease and host-versus-graft rejection for broader patient access.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Cell-based immunotherapy, specifically chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapies, represents a promising avenue for next-generation cancer treatment.
  • Allogeneic 'off-the-shelf' CAR-T cell products offer manufacturing, storage, and distribution advantages for treating a large patient population.
  • Current limitations in allogeneic CAR-T cell therapy development include the significant risks of graft-versus-host disease (GvHD) and host-versus-graft (HvG) allorejection.

Purpose of the Study:

  • To review genetic engineering strategies aimed at enhancing antitumor efficacy and safety of CAR-T cell therapies.
  • To discuss methods for mitigating GvHD and HvG allorejection in allogeneic CAR-T cell products.
  • To explore the challenges and prospects of these genetic engineering approaches for advancing universal cell-based cancer immunotherapy.

Main Methods:

  • Review of existing literature on genetic engineering strategies for CAR-T cell therapy.
  • Analysis of techniques designed to improve CAR-T cell antitumor activity.
  • Examination of genetic modifications to reduce immunogenicity and allorejection.

Main Results:

  • Various genetic engineering strategies have been implemented to improve CAR-T cell therapy efficacy and safety.
  • These strategies aim to reduce the incidence of GvHD and HvG allorejection, key barriers to allogeneic CAR-T cell product development.
  • Progress in genetic engineering holds promise for overcoming current limitations in T-cell based immunotherapies.

Conclusions:

  • Genetic engineering is crucial for advancing allogeneic CAR-T cell therapies towards a universal cancer immunotherapy.
  • Addressing GvHD and HvG is essential for the successful translation of 'off-the-shelf' cell products.
  • Continued research and development in genetic engineering strategies are vital for expediting clinical adoption and expanding patient access to CAR-T cell treatments.
Keywords:
CRISPR-Cas9allogeneic cell productsalloreactivitycancer immunotherapychimeric antigen receptor-engineered T (CAR-T) cellsgene engineeringgraft-versus-host diseaseimmune checkpoints

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