Cluster of Differentiation 5 (CD5) (CD5)

Cluster of Differentiation 5 (CD5) is a 67 kDa Type I transmembrane glycoprotein belonging to the scavenger receptor cysteine-rich (SRCR) superfamily (UniProt P06127). It is constitutively expressed on all mature T cells and a small subset of B cells known as B-1 cells (PubMed: 28811300). Biologically, CD5 acts as a negative regulator of T-cell receptor (TCR) and B-cell receptor (BCR) signaling, helping to fine-tune immune responses and maintain self-tolerance (PubMed: 31515258). In oncology, CD5 is highly expressed in various malignancies, including T-cell acute lymphoblastic leukemia (T-ALL), peripheral T-cell lymphoma (PTCL), and certain B-cell malignancies like chronic lymphocytic leukemia (CLL) (PubMed: 30249788). Because of its near-universal expression on malignant T cells, it is an attractive target for immunotherapy, including monoclonal antibodies and CAR-T cell therapies (ClinicalTrials.gov: NCT03081910). Therapeutic strategies often involve the use of anti-CD5 CAR-T cells or immunotoxins to selectively deplete malignant populations. However, targeting CD5 presents unique challenges, such as 'fratricide' where CAR-T cells attack each other due to their own CD5 expression. Additionally, successful depletion of CD5-positive cells can lead to profound T-cell aplasia and increased susceptibility to infections. Despite these risks, CD5 remains a high-priority target for refractory T-cell malignancies where few other options exist.

Other names

T1Leu-1Lymphocyte antigen CD5T-cell surface glycoprotein CD5

Drugs targeting CD5 typically utilize monoclonal antibodies, immunotoxins, or chimeric antigen receptor (CAR) T-cells to induce direct cell lysis, antibody-dependent cellular cytotoxicity (ADCC), or deliver cytotoxic payloads to CD5-expressing malignant cells (PubMed: 31515258, ClinicalTrials.gov: NCT03081910).