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Generation of Human Chimeric Antigen Receptor Regulatory T Cells
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Genome-edited allogeneic donor "universal" chimeric antigen receptor T cells
1UCL Great Ormond Street Institute of Child Health, Zayed Centre for Research, London, United Kingdom.
Blood
|October 12, 2022
Summary
Chimeric antigen receptor (CAR) T-cell therapies offer promise for blood cancers. Genome editing advances are enabling allogeneic CAR T-cells by overcoming HLA barriers, potentially reducing costs and improving accessibility.
Area of Science:
- Immunology
- Oncology
- Gene Editing
Background:
- Chimeric antigen receptor (CAR) T-cell therapies, specifically alpha-beta T-cell receptor (TCRαβ) CAR T-cells, are approved for certain B-cell malignancies.
- Current autologous CAR T-cell therapy is expensive and logistically complex, limiting patient access.
- Allogeneic, or donor-derived, CAR T-cell banks could expand therapeutic reach if HLA-mismatch issues are resolved.
Purpose of the Study:
- To explore the potential of allogeneic donor-derived CAR T-cells to overcome limitations of autologous therapies.
- To highlight the role of genome editing in addressing HLA-mismatch barriers in T-cell therapy.
- To discuss advancements in editing technologies and their application in treating a broader range of blood cancers.
Main Methods:
- Utilizing genome editing technologies, including CRISPR/Cas9 and base editing, to disrupt TCRαβ and prevent graft-versus-host disease.
- Employing multiplexed editing strategies to target HLA molecules, shared antigens, and immune checkpoint pathways.
- Conducting clinical trials to evaluate safety, efficacy, and durability of allogeneic CAR T-cell therapies.
Main Results:
- Genome editing technologies are advancing, with CRISPR/Cas9 and base editing in clinical trials for allogeneic T-cell therapies.
- Multiplexed editing enhances the potential to target multiple factors, including HLA molecules and antigens.
- Clinical trials are underway to establish safety and response durability for these novel therapies.
Conclusions:
- Genome editing is crucial for overcoming allogeneic barriers in CAR T-cell therapy, particularly for preventing graft-versus-host disease.
- Advancements in editing technologies are expanding the applicability of CAR T-cells to more blood malignancies.
- Future clinical trials will determine the safety, efficacy, and optimal use of allogeneic CAR T-cells, including their potential role alongside allogeneic transplantation.
