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Updated: Sep 9, 2025
A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
Recent advances in universal chimeric antigen receptor T cell therapy.
Ning Jiang1, Zhaoyi Yang1, Huilei Miao1
1National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Universal CAR-T (UCAR-T) cell therapy offers an accessible "off-the-shelf" treatment for blood cancers. Advances in gene editing and alternative cell sources are overcoming immune barriers like graft-versus-host disease, improving safety and efficacy.
Area of Science:
- Immunology
- Cellular Therapy
- Gene Editing
Background:
- Chimeric antigen receptor (CAR) T cell therapy shows high efficacy for hematological malignancies but faces manufacturing complexity.
- Universal CAR-T (UCAR-T) cells from allogeneic donors present an
- off-the-shelf
- alternative, yet face immunological barriers: graft-versus-host disease (GvHD) and host-versus-graft rejection (HvGR).
Purpose of the Study:
- To review recent advancements in UCAR-T cell engineering and clinical strategies to enhance safety and efficacy.
- To explore methods for overcoming immunological barriers and improving UCAR-T cell function and persistence.
Main Methods:
- Gene-editing technologies (CRISPR/Cas9, base editors) to ablate T cell receptor (TCR) and disrupt human leukocyte antigen (HLA) expression.
- Development of UCAR-T products from alternative cell sources like γδ T cells.
- Multifaceted approaches to augment UCAR-T cell function, including tumor microenvironment (TME) modulation and overcoming tumor heterogeneity.
Main Results:
- Gene editing successfully prevents GvHD and evades HvGR, improving UCAR-T safety.
- Alternative cell sources and enhanced functional augmentation strategies show promise for UCAR-T efficacy.
- Clinical trials demonstrate promising efficacy in hematological malignancies, with ongoing challenges in solid tumors.
Conclusions:
- Sophisticated cellular engineering and innovative clinical strategies are crucial for realizing the potential of UCAR-T therapy.
- Integration of enhanced lymphodepletion, combination therapies, and alternative administration routes will be essential for widespread UCAR-T accessibility and potency.
