Intercellular Adhesion Molecule 1 and Decay-Accelerating Factor (CD55) (ICAM-1/DAF)

Intercellular Adhesion Molecule 1 (ICAM-1) and Decay-Accelerating Factor (DAF, or CD55) function as the dual-receptor system for Coxsackievirus A21 (CVA21), an enterovirus being developed as an oncolytic immunotherapy (Shafren et al., 1997, J. Virol.). ICAM-1 is a transmembrane protein typically involved in leukocyte trafficking and inflammatory signaling, while DAF is a complement-regulating protein that protects host cells from complement-mediated damage (UniProt P05362, P08174). In many cancers, such as melanoma and lung adenocarcinoma, both ICAM-1 and DAF are significantly upregulated, making these cells highly susceptible to CVA21 infection (Viralytics, 2018). The virus utilizes DAF for initial cell surface attachment and ICAM-1 for internalization and uncoating, leading to selective viral replication and subsequent lysis of the cancer cell. This mechanism, utilized by the drug candidate V937 (Cavatak), not only destroys the primary tumor but also promotes an abscopal effect by stimulating the immune system to recognize tumor antigens released during lysis (Annals of Oncology, 2015).

Other names

CD54CD55CVA21 Receptor ComplexComplement decay-accelerating factorMajor group rhinovirus receptor

Oncolytic viral entry and replication mediated by ICAM-1 and DAF binding, leading to immunogenic cell death and systemic anti-tumor immunity.