The present invention can provide an anti-CD40 monoclonal antibody based onthe monoclonal antibody deposited under accession No. FERM BP-7759 at theNationalInstitute of Advanced Industrial Science and Technology, and which comprisesalaninesubstitutions at positions 234 and 237 and a serine substitution at position331 of theheavy chain constant region (based on the numbering of the EU index of Kabatet al.Sequences of proteins of Immunological Interest, 1991, Fifth edition) relativeto thedeposited monoclonal antibody. This monoclonal antibody has an agonistactivity forCD40 and has increased plasma residence time as well as decreased livertoxicityrelative to an antibody not having alanine substitutions at positions 234 and237.
