The present inventors succeeded in producing: an anti-Epiregulin antibody exhibiting a cross-species reactivity between a non-human animal crab-eating monkey and a human animal an anti-Epiregulin antibody with suppressed chemical decomposition an anti-Epiregulin antibody having a lowered isoelectric point an anti-Epiregulin antibody having an elevated thermal denaturation midpoint temperature and an anti-Epiregulin antibody having a reduced amount of aggregates, by appropriately substituting an amino acid residue in the variable region sequence of a humanized EP27 antibody that is capable of exhibiting a cytotoxic activity and neutralization activity on a cancer cell, said cancer cell expressing human Epiregulin, to thereby inhibit the proliferation of the cancer cell. Also, the present inventors succeeded in creating a therapeutic agent for non-small-cell lung carcinoma excluding adenocarcinoma, said therapeutic agent comprising one of the aforesaid antibodies as an active ingredient.本發明人等經由對表現人Epiregulin之癌細胞發揮細胞毒性及中和活性而抑制癌細胞增殖之人源化EP27抗體的變異區的序列中的胺基酸殘基進行適當地取代,成功地做出顯示非人動物之食蟹猿與人的動物間的種間交叉反應之抗Epiregulin抗體、化學分解受到抑制的抗Epiregulin抗體、等電點下降的抗Epiregulin抗體、熱變性中間溫度上升的抗Epiregulin抗體、締合體量減少的抗Epiregulin抗體,成功地做出含有以該抗體作為有效成分之腺癌以外的非小細胞肺癌之治療劑。
