A humanized antibody that binds to the interleukin 2 receptor

Area of Science:

• Immunology
• Biotechnology
• Molecular Biology

Background:

• The anti-Tac monoclonal antibody targets the p55 chain of the human interleukin 2 receptor.
• It inhibits T cell proliferation by blocking interleukin 2 binding.
• Murine antibodies like anti-Tac can elicit an immune response in humans, limiting therapeutic use.

Purpose of the Study:

• To engineer a humanized anti-Tac antibody with reduced immunogenicity.
• To retain the binding affinity and inhibitory function of the original murine antibody.

Main Methods:

• Constructed a humanized antibody by grafting complementarity-determining regions (CDRs) of murine anti-Tac onto human framework and constant regions.
• Selected human framework regions for maximal sequence homology.
• Utilized a computer model to identify and retain critical murine amino acids outside the CDRs that interact with the CDRs or antigen.

Main Results:

• The humanized anti-Tac antibody retains binding to the p55 chain of the interleukin 2 receptor.
• The engineered antibody exhibits an affinity of 3 x 10(9) M-1 for p55.
• This affinity is approximately one-third of that of the original murine anti-Tac antibody.

Conclusions:

• Humanization of the anti-Tac antibody is feasible, potentially reducing immune responses.
• The humanized antibody maintains significant, though reduced, binding affinity for its target.
• Further studies are warranted to assess the in vivo efficacy and immunogenicity of the humanized antibody.