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Updated: Jun 28, 2025

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates

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Engineering immune-evasive allogeneic cellular immunotherapies.

Karen E Martin^1,2, Quirin Hammer³, Karlo Perica^4,5

¹Precision Immunotherapy Alliance, The University of Oslo, Oslo, Norway.

Nature Reviews. Immunology

|April 24, 2024

Summary

Allogeneic cell therapies offer promising cancer treatments but face immune rejection. Strategies inspired by viral and cancer immune evasion can improve the persistence of these off-the-shelf immunotherapies.

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Area of Science:

Immunology
Oncology
Biotechnology

Background:

Allogeneic cellular immunotherapies present a scalable and cost-effective approach to cancer treatment.
Immune rejection of transferred allogeneic T cells and natural killer (NK) cells limits their clinical efficacy compared to autologous therapies.
Overcoming immune rejection is crucial for realizing the full potential of off-the-shelf cell-based cancer treatments.

Purpose of the Study:

To discuss strategies for engineering allogeneic T and NK cells to evade immune rejection.
To explore the use of viral and cancer immune escape mechanisms as a basis for enhancing cell therapy persistence.
To highlight the role of genome editing and synthetic biology in developing advanced cell-based immunotherapies.

Main Methods:

Review of immune evasion mechanisms employed by viruses and cancer cells.
Discussion of genome editing and synthetic biology approaches for cell engineering.
Analysis of innate and adaptive immune responses in the context of allogeneic cell therapy.

Main Results:

Identification of immune evasion strategies that can be adapted for allogeneic cell therapies.
Potential for improving the persistence and therapeutic window of off-the-shelf cell products.
Emphasis on the need to consider host immune responses for successful therapeutic outcomes.

Conclusions:

Engineering allogeneic cells with immune-evasive properties is key to overcoming rejection barriers.
Viral and cancer immune escape mechanisms provide valuable blueprints for enhancing cell therapy persistence.
Precision immunotherapy design requires a comprehensive understanding of recipient immune responses to maximize therapeutic benefit.