Abstract
T lymphocytes are indispensable for the host systems of defense against pathogens, tumors, and environmental threats. The therapeutic potential of harnessing the cytotoxic properties of T lymphocytes for antigen-specific cell elimination is both evident and efficacious. Genetically engineered T-cells, such as those employed in CAR-T and TCR-T cell therapies, have demonstrated significant clinical benefits in treating cancer and autoimmune disorders. However, the current landscape of T-cell genetic engineering is dominated by strategies that necessitate in vitro T-cell isolation and modification, which introduce complexity and prolong the development timeline of T-cell based immunotherapies. This review explores the complexities of gene delivery systems designed for T cells, covering both viral and nonviral vectors. Viral vectors are known for their high transduction efficiency, yet they face significant limitations, such as potential immunogenicity and the complexities involved in large-scale production. Nonviral vectors, conversely, offer a safer profile and the potential for scalable manufacturing, yet they often struggle with lower transduction efficiency. The pursuit of gene delivery systems that can achieve targeted gene transfer to T cell without the need for isolation represents a significant advancement in the field. This review assesses the design principles and current research progress of such systems, highlighting the potential for in vivo gene modification therapies that could revolutionize T-cell based treatments. By providing a comprehensive analysis of these systems, we aim to contribute valuable insights into the future development of T-cell immunotherapy.
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Abbreviations
- aAPC:
-
Artificial antigen-presenting cell
- AAV:
-
Adeno-associated virus
- ABE:
-
Adenine base editor
- BCMA:
-
B-cell maturation antigen
- CAR-T therapy:
-
Chimeric antigen receptor T-cell therapy
- CBE:
-
Cytosine base editor
- CD19:
-
The cluster of differentiation 19
- CPPs:
-
Cell-penetrating peptides
- CRISPR:
-
Clustered regularly interspaced short palindromic repeats
- CRS:
-
Cytokine release syndrome
- CTL:
-
Cytotoxic T lymphocyte
- DARPins:
-
Designed ankyrin repeat proteins
- EBV:
-
Epstein-Barr virus
- EGFR:
-
Epidermal growth factor receptor
- FDA:
-
Food and drug administration
- HDR:
-
Homology-directed repair
- HIV:
-
Human immunodeficiency virus
- ITR:
-
Inverted terminal repeat
- LDLR:
-
Low-density lipoprotein receptor
- LNP:
-
Lipid nanoparticle
- LV:
-
Lentiviral vector
- MHC:
-
Major histocompatibility complex
- PB:
-
PiggyBac transposon system
- RME:
-
Receptor-mediated endocytosis
- SB system:
-
Sleeping Beauty transposon system
- TAA:
-
Tumor-associated antigen
- TCR-T therapy:
-
T-cell receptor engineered T-cell therapy
- TIL therapy:
-
Tumor-infiltrating lymphocyte therapy
- VSV-G:
-
Vesicular stomatitis virus G protein
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Wang, F., Huang, Y., Li, J. et al. Targeted gene delivery systems for T-cell engineering. Cell Oncol. (2024). https://doi.org/10.1007/s13402-024-00954-6
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DOI: https://doi.org/10.1007/s13402-024-00954-6