The present inventors appropriately changed the amino acid residues in the variable region sequence of the humanized EP27 antibody that inhibits the growth of cancer cells by exerting cytotoxic activity and neutralizing activity against cancer cells expressing human Epiregulin. Anti-Epiregulin antibody showing species cross-reactivity between non-human cynomolgus monkeys and human animals by substitution, anti-Epiregulin antibody with suppressed chemical degradation, anti-Epiregulin antibody with reduced isoelectric point, intermediate heat denaturation An anti-Epiregulin antibody with an increased temperature and an anti-Epiregulin antibody with a reduced amount of aggregate were produced, and a therapeutic agent for non-small cell lung cancer other than adenocarcinoma containing the antibody as an active ingredient was successfully produced.本発明者らは、ヒトEpiregulinを発現する癌細胞に対して細胞傷害活性および中和活性を発揮することによって癌細胞の増殖を阻害するヒト化EP27抗体の可変領域配列中のアミノ酸残基を適宜置換することによって、非ヒト動物であるカニクイザルおよびヒト動物間の種交差反応性を示す抗Epiregulin抗体、化学的分解が抑制された抗Epiregulin抗体、等電点が低下した抗Epiregulin抗体、熱変性中間温度が上昇した抗Epiregulin抗体、会合体量の低減された抗Epiregulin抗体を作出し、当該抗体を有効成分として含む腺癌以外の非小細胞肺癌の治療剤を作出することに成功した。
