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A2CAR5

Development stage
Preclinical
Lead developer
Seoul National University
Modality
CRISPR-Cas9 → CRISPR Systems → Programmable Nucleases → Gene Editing → Gene Therapies, CAR-T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies
Administration
Intravenous
01

Overview

A2CAR5 is a high-affinity chimeric antigen receptor (CAR) T-cell therapy targeting the CD5 antigen, specifically developed for the treatment of CD5-positive T-cell malignancies such as T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphoma (PTCL). Because CD5 is naturally expressed on healthy T cells, A2CAR5 initially faced significant challenges with fratricide (self-killing) and excessive cytokine release during manufacturing. To resolve these issues, the therapy utilizes CRISPR/Cas9 gene editing to knock out the endogenous CD5 gene, which prevents fratricide and reduces T-cell exhaustion. Furthermore, the TRAC (T-cell receptor alpha constant) gene is knocked out to create an allogeneic, "off-the-shelf" platform. Compared to lower-affinity constructs like C7CAR5, A2CAR5 demonstrates superior cytotoxic engagement and functional persistence against CD5-positive malignant cells once the fratricide mechanism is mitigated.

Other names
anti-CD5 CAR-T (high affinity)high-affinity anti-CD5 CAR-T
02

Targets

CD5 (T-cell surface glycoprotein CD5)

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