細胞表面的異常醣化(glycosylation)經常伴隨細胞的癌化(oncogensis) 現象發生。目前已有許多腫瘤相關的醣抗原會表現在各式的人類癌細胞的細胞表面上，如GM2, GD2, GD3, fucosyl GM1, STn 及 Globo H，因而這些醣抗原也成為潛在的癌症治療標的。在本篇報告中，我們的主要研究標的是醣抗原Globo H，Globo H最早是從人類乳癌細胞株MCF-7分離出來的，並且是以與神經醯胺鍵結(ceramide-linked)成醣脂質(glycolipid)的形式存在，目前也是正在進行臨床試驗驗證中的腫瘤治療標的（現有一以醣抗原Globo H為癌症治療性疫苗在乳癌病患進行2/3期的臨床試驗中）。本研究的目標是開發一可專一性辨認醣抗原Globo H的人源化治療性抗體並可作為乳癌治療的應用。在此報告中，我們建立一株人源化anti-Glbo H抗體DCBPR0801並進行此抗體在生物體外(in vitro)及生物體內(in vivo)對人類乳癌細胞的細胞毒殺作用的評估。我們發現人源化的DCBPR0801抗體不僅維持其對醣抗原Gobo H的親和性結合力，並且也保有抗體Fc-dependent的細胞毒殺能力，包括對人類乳癌細胞具有補體誘發的細胞毒性(CDC)，及抗體依賴性細胞介導的細胞毒性(ADCC)。我們更進一步在乳癌異體移植動物模式研究中發現，當DCBPR0801與人類PBMC合併作用時，DCBPR0801確實能有效的抑制腫瘤的生長。本研究顯示DCBPR0801的抗乳癌細胞作用，有望在未來可進一步開發成癌症治療製劑。
Oncogenesis is often associated with aberrant glycosylation changes in the cell surface. Several of these tumor-associated carbohydrate antigens, including GM2, GD2, GD3, fucosyl GM1, STn and Globo H, were expressed in many human carcinomas and may serve as potential targets for cancer therapy. In this report, we focus on the Globo H antigen that is a hexasaccharide originally isolated as a ceramide-linked glycolipid from the human breast cancer cell line MCF-7 and a clinically validating target (ex. A phase 2/3 trail of Globo H cancer therapeutic vaccine for breast cancer patient is ongoing). The aim of this study is to develop a humanized therapeutic antibody specifically against Globo H for breast cancer therapy. Here we generated a humanized anti-Globo H antibody DCBPR1101 and evaluated its cytotoxic effect on breast cancer cells in vitro and in vivo. We also report that DCBPR1101 remained its binding affinity to Globo H and possessed antibody Fc-dependent cytotoxicity activities, including complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC), on breast cancer cells. In addition, we observed that DCBPR1101 when co-administrated with human PBMC effectively inhibited tumor outgrowth in breast cancer xenograft model. This study provides insight into the basis for the anti-tumor properties of DCBPR1101 in breast cancer and will be useful for further cancer therapeutic development