抗中皮腫活性を示す二重特異性抗体の薬効評価

• Published in: 日本薬理学会年会要旨集 p. 1-SS-56
• Main Authors: 金守, 悠希, 森脇, 康博, 瀧本, 姿子, 三澤, 日出巳, 今井, 浩三, 辻, 祥太郎
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2020
• Subjects: antibody; antibody-dependent cell cytotoxicity; cancer
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.93.0_1-SS-56

Malignant mesothelioma is a fatal tumor caused by past exposure to asbestos. In Japan, mesothelioma due to asbestos exposure is a major public health problem. The prognosis for mesothelioma patients is very poor. Satisfactory recovery is often not possible with chemotherapy and/or radiotherapy. Therefore, a new effective anti-mesothelioma drug is urgently required. In previous study, we isolated a highly specific anti-mesothelioma mAb, SKM9-2. The specificity and sensitivity of SKM9-2 to mesothelioma reach 99% and 92%, respectively. SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1), a novel mucin-like membrane protein. In this study, we investigated the cytotoxic activity of bispecific antibodies (bsAbs) in which the antigen-recognition domains of SKM9-2 and anti-CD3 (OKT3) were linked. BsAbs were purified from the culture supernatant of stably expressed mammalian cell lines and were analyzed about the binding to SKM9-2 epitope and CD3. Some bsAbs strongly bound to SKM9-2 epitope but not CD3. In these bsAbs, two antigen recognition domains may interfere. A bsAb that bound to both SKM9-2 epitope and CD3 showed a strong T cell-dependent cytotoxicity against mesothelioma. SKM9-2 binds to mesothelioma cells but not normal tissues. Thus, T cell-engaging bsAb including SKM9-2 may be a promising drug for mesothelioma.