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C-kit Targeted Radioimmunotherapy of Small Cell Lung Cancer in Nude Mice using Anti-c-kit Antibodies
https://repo.qst.go.jp/records/64266
https://repo.qst.go.jp/records/64266cc28a14d-f5e2-42f5-a890-3699c37f4be2
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-07-08 | |||||
| タイトル | ||||||
| タイトル | C-kit Targeted Radioimmunotherapy of Small Cell Lung Cancer in Nude Mice using Anti-c-kit Antibodies | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Yoshida, Chisato
× Yoshida, Chisato× Tsuji, Atsushi× Koizumi, Mitsuru× Arano, Yasushi× Saga, Tsuneo× 吉田 千里× 辻 厚至× 小泉 満× 荒野 泰× 佐賀 恒夫 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | C-kit is a tyrosine kinase-type receptor for the stem cell factor. C-kit is highly expressed in some cancers such as gastrointestinal stromal tumors and small cell lung cancer (SCLC), in which autocrine/paracrine mechanisms stimulate tumor growth. SCLC, representing about 20% of all lung cancer types, is an aggressive form of lung cancers and tends to develop metastases to lymph nodes and other organs at an early stage. Although SCLC is sensitive to chemotherapy and radiation, the overall prognosis remains poor, and the development of effective therapies is needed for SCLC patients. In this study, the potential of two anti-c-kit monoclonal antibodies (Mab1 and Mab2) for the radioimmunotherapy of SCLC was evaluated in mouse model. Methods: Mabs were conjugated with CHX-A-DTPA and were labeled with 111In and 90Y. Cell binding, competitive inhibition and internalization assays were performed using 111In-labeled Mabs and a human SCLC cell line, SY, highly expressing c-kit. Biodistribution study of 111In-labeled Mabs was performed using nude mice bearing SY tumors. Therapeutic efficacy was also estimated after injecting 90Y-labeled Mabs (0, 20, 50 or 100 Ci) to SY-bearing mice and subsequent measuring the tumor size of SY-bearing mice twice a week until day 30. Results: In vitro studies showed that 111In-labeled Mabs specifically bound to SY cells with high affinities and were quickly internalized into cells after binding to c-kit. Biodistribution studies showed that tumor uptake of 111In-labeled Mab1 and Mab2 at maximum were 23.3+/-2.3 and 31.5+/-7.7 %ID/g, respectively. Administration of 90Y-labeled Mabs was well tolerated by all mice. 90Y-labeled Mab1 and Mab2 showed dose-dependent therapeutic effect, in which the administration of 100 Ci of 90Y-labeled Mabs significantly suppressed tumor growth including complete disappearance of the tumor in most mice. Conclusion: These 90Y-labeled anti-c-kit Mabs have the potential for radioimmunotherapy of c-kit-expressing SCLC. | |||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | The International Chemical Congress of Pacific Basin Societies （2010 Pacifichem） | |||||
| 発表年月日 | ||||||
| 日付 | 2010-12-20 | |||||
| 日付タイプ | Issued | |||||
