Multispecific binding proteins that bind to HER2, NKG2D receptor, and CD16 are described, as well as pharmaceutical compositions and therapeutic methods useful for treating cancer. Patients with HER2 overexpressing breast cancer have substantially lower overall survival and shorter disease free duration than patients whose cancer does not overexpress HER2. HER2 overexpression includes aggressive forms of uterine cancer, such as breast, ovarian, esophageal, bladder and stomach, salivary duct, adenocarcinoma of the lung, and serous endometrial cancer of the uterus. It is also known to cause many other types of cancer. The multispecific binding proteins disclosed herein provide a means by which such cancers can be treated.ＨＥＲ２、ＮＫＧ２Ｄ受容体、およびＣＤ１６に結合する多重特異性結合タンパク質、ならびにがんの処置に有用な医薬組成物および治療方法が記載される。ＨＥＲ２過発現乳がんを有する患者は、がんがＨＥＲ２を過発現していない患者よりも実質的に低い全生存率および短い無病期間を有する。ＨＥＲ２の過発現は、乳がん、卵巣がん、食道がん、膀胱がんおよび胃がん、唾液管癌、肺の腺癌ならびに子宮漿液性内膜癌などの侵襲性の形態の子宮がんが挙げられる、多数の他の種類のがんを生じることも公知である。本願に開示される多重特異性結合タンパク質は、このようながんを処置し得る手段を提供する。
