Camrelizumab exhibits dual specificity implications for antitumor immunity

Introduction. Camrelizumab is a high-affinity monoclonal antibody targeting programmed cell death protein 1 (PD-1) that has demonstrated strong clinical activity across multiple solid tumors. Emerging evidence suggests that camrelizumab can bind not only PD-1 but also the stress-induced ligand ULBP2 which activates natural killer (NK) and CD8+-T cells. Aim. To experimentally verify specific camrelizumab binding to ULBP2 (in contrast to reference anti-PD-1 antibodies pembrolizumab, nivolumab, and prolgolimab), compare anti-PD-1 antibodies binding profiles, and explore the potential immunological implications of camrelizumab dual specificity to PD-1 and ULBP2 in the context of antitumor immune response. Materials and methods. Binding interactions between ULBP2 and the four anti-PD-1 antibodies (camrelizumab, pembrolizumab, nivolumab, and prolgolimab) were assessed using surface plasmon resonance and flow cytometry. Results. Among all the tested antibodies, only camrelizumab exhibited specific binding to ULBP2 (KD (equilibrium dissociation constant) = 2.79 × 10–7 M). This interaction was confirmed by two independent methods. Conclusion. Camrelizumab displays a unique dual specificity for PD-1 and ULBP2 maintaining activity of effector lymphocytes and potentially decreases the dependence of therapy efficacy of PD-1 ligand (PD-L1) expression level. These findings expand our understanding of the biological features of camrelizumab and support its potential as an immunomodulator with broadened activity.