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 (K_D (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.