Active immunization with Tocilizumab mimotopes induces specific immune responses.

Area of Science:

• Immunology
• Biotechnology
• Drug Discovery

Background:

• Tocilizumab is a monoclonal antibody that targets interleukin-6 receptor (IL-6R), inhibiting pro-inflammatory IL-6 signaling.
• Practical limitations of therapeutic antibodies necessitate the development of alternative strategies.
• Phage display technology offers a method for generating epitope mimics of therapeutic proteins.

Purpose of the Study:

• To generate Tocilizumab-specific epitope mimics using phage display.
• To evaluate the ability of these peptide mimics to induce humoral and cellular immune responses in vivo.
• To assess the potential of mimotopes as alternatives to therapeutic antibodies.

Main Methods:

• Phage display peptide library screening was employed to identify Tocilizumab epitope mimics.
• Identified mimotopes were conjugated to carrier proteins (e.g., KLH) for immunization.
• Humoral responses were assessed by measuring antibody binding to IL-6R and cellular responses via STAT3/Erk signaling and ADCC assays in immunized mice.

Main Results:

• Four peptide sequences were identified as Tocilizumab epitope mimics.
• Immunization with mimotope-carrier conjugates elicited specific antibodies that bound to IL-6R on various cell lines and primary cells.
• The induced antibodies demonstrated the ability to reduce STAT3 and Erk signaling pathways and mediate antibody-dependent cellular cytotoxicity (ADCC).

Conclusions:

• Successfully isolated four Tocilizumab mimotopes using phage display.
• These mimotopes induced specific humoral and cellular immune responses in vitro and in vivo.
• The findings suggest that Tocilizumab mimotopes can serve as potential alternatives for inducing therapeutic immune responses.