CD44 antigen variant 3 (CD44v3)

CD44v3 is a variant isoform of the CD44 transmembrane glycoprotein, generated through the alternative splicing of exon v3. Unlike the standard CD44 isoform (CD44s), the v3 variant is uniquely modified with heparan sulfate side chains, which allows it to function as a co-receptor by sequestering and presenting heparin-binding growth factors, such as fibroblast growth factor-2 (FGF-2) and hepatocyte growth factor (HGF), to their cognate receptor tyrosine kinases (https://www.uniprot.org/uniprotkb/P16070/entry, PMID: 15150570). This interaction significantly enhances signaling pathways involved in cell proliferation, survival, and migration. In oncology, CD44v3 is highly overexpressed in various solid tumors, particularly squamous cell carcinomas of the head, neck, and lung, where it serves as a marker for cancer stem cells and promotes metastatic potential (PMID: 24706598, PMID: 32541818). Because its expression is relatively restricted in normal tissues compared to tumor tissues, it is a primary target for specialized therapies including monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapies (PMID: 31085023). Therapeutic development focuses on disrupting the growth-factor-binding niche or directly eliminating CD44v3-positive cells to inhibit tumor progression and overcome drug resistance.

Other names

CD44 isoform 3Phagocytic glycoprotein 1 variant 3Hereditary erythrocyte membrane glycoprotein variant 3Extracellular matrix receptor III variant 3Hermes antigen variant 3Epican (when combined with v3-v10)HCAM variant 3

Targeted cell lysis via CAR-T cells; Antibody-dependent cellular cytotoxicity (ADCC); Blockade of growth factor sequestration and presentation to RTKs