抗癌藥物新發展：抗體－藥物複合體於癌症的治療應用

Antibody-Drug Conjugates for Cancer Therapy

10.6880/TJON.202112_21(2).02

林蓉萱(Rong-Shiuan Lin)；陳幼貴(Yu-Kuei Chen)；陳怡君(I-Chun Chen)

抗體－藥物複合體 ； HER2－陽性乳癌 ； 三陰性乳癌 ； Antibody-drug conjugate ； HER2-positive breast cancer ； Triple-negative breast cancer

腫瘤護理雜誌

21卷2期（2021 / 12 / 01）

13 - 19

繁體中文

抗體－藥物複合體（Antibody-drug conjugate）是目前相對較新型的抗癌藥物治療。抗體－藥物複合體是由抗體、細胞毒性藥物及將二者結合的連接頭共三部分所組合而成的藥物。截至目前美國FDA核准之抗體－藥物複合體共有11種，其中就有2種抗體－藥物複合體之適應症是針對HER2陽性乳癌治療的trastuzumab emtansine及trastuzumab deruxtecan。另外1種適應症為三陰性轉移性乳癌治療的sacituzumab govitecan。抗體－藥物複合體與傳統化學治療不同的是，藉由抗體具有對標地細胞抗原之專一選擇性作用，引導進入癌細胞之後，連接頭經過分解再把結合在抗體上的細胞毒性藥物釋放出來，直接到達癌細胞，進而產生抗癌治療效果。不僅降低正常細胞的傷害及全身性副作用，更能提高抗癌療效。因此，有關抗體－藥物複合體的技術開發及臨床試驗研究相當熱門，期待未來增加更多癌症適應症，應用在相關癌症病人身上。

Antibody-drug conjugates are currently the new types of anticancer drug therapy. Antibody-drug complex is a drug composed of three parts: an antibody, a cytotoxic drug, and a linker. There are 11 types of antibody-drug conjugates approved by the US FDA. Trastuzumab emtansine and trastuzumab deruxtecan are indicated for the treatment of HER2-positive breast cancer. Sacituzumab govitecan is approved for the treatment of metastatic triple-negative breast cancer. The difference between the antibody-drug conjugates and traditional chemotherapy is that the antibody is specific for the target cell antigen. After it is guided into the cancer cells, the linker is destructed and then the cytotoxic drug bound to the antibody is released. It directly reaches the cancer cells and produces anti-cancer effects. It not only reduces normal cell damage and systemic side effects, but also improves anti-cancer efficacy. Therefore, the technology innovation and clinical trial research for antibody-drug conjugates are quite popular. We are expecting more ADC indications for cancer treatment in the future.

1. Bardia, A.,Hurvitz, S. A.,Tolaney, S. M.,Loirat, D.,Punie, K.,Oliveira, M.,Brufsky, A.,Sardesai, S. D.,Kalinsky, K.,Zelnak, A. B.,Weaver, R.,Traina, T.,Dalenc, F.,Aftimos, P.,Lynce, F.,Diab, S.,Cortés, J.,O’Shaughnessy, J.,Diéras, V.,Rugo, H. S.(2021).Sacituzumab govitecan in metastatic triple-negative breast cancer.The New England Journal of Medicine,384(16),1529-1541.
2. Birrer, M. J.,Moore, K. N.,Betella, I.,Bates, R. C.(2019).Antibody-drug conjugate-based therapeutics: State of the science.Journal of The National Cancer Institute,111(6),538-549.
3. Chau, C. H.,Steeg, P. S.,Figg, W. D.(2019).Antibody-drug conjugates for cancer.The Lancet,394(10200),793-804.
4. Criscitiello, C.,Morganti, S.,Curigliano, G.(2021).Antibody-drug conjugates in solid tumors: A look into novel targets.Journal of Hematology & Oncology,14(1),1-18.
5. Drugs@FDA: FDA-Approved Drugs. U. S. Food and Drug Administration. Retrieved September 10, 2021, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761139s011lbl.pdf
6. Drugs@FDA: FDA-Approved Drugs. U. S. Food and Drug Administration. Retrieved September 10, 2021, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761115s000lbl.pdf
7. Drugs@FDA: FDA-Approved Drugs. U. S. Food and Drug Administration. Retrieved September 10, 2021, from https://www.https://www.kadcyla.com/content/dam/gene/kadcyla/patient/pdfs/downloads/kadcyla_prescribing.pdf
8. Makawita, S.,Meric-Bernstam, F.(2020).Antibody-drug conjugates: Patient and treatment selection.American Society of Clinical Oncology Educational Book,40,105-114.
9. Modi, S.,Saura, C.,Yamashita, T.,Park, Y. H.,Kim, S. B.,Tamura, K.,Andre, F.,Iwata, H.,Ito, Y.,Tsurutani, J.,Sohn, J.,Dendu luri, N.,Perrin,C.,Aogi, K.,Tokunaga, E.,Im, S. -A.,Lee, K. S.,Hurvitz, S.A.,Cortes, J.,Krop, I.(2020).Trastuzumab deruxtecan in previously treated HER2-Positive breast cancer.The New England Journal of Medicine,382(7),610-621.
10. Nakada, T.,Sugihara, K.,Jikoh, T.,Abe, Y.,Agatsuma, T.(2019).The latest research and development into the antibody-drug conjugate.uzumab deruxtecan (DS-8201a), for HER2 Cancer therapyChemical and Pharmaceutical Bulletin,67(3),173-185.
11. Schwartz, R. S.(2004).Paul Ehrlich’s Magic Bullets.The New England Journal of Medicine,320(11),1079-1080.
12. Thomas, A.,Teicher, B. A.,Hassan, R.(2016).Antibody–drug conjugates for cancer therapy.The Lancet Oncology,17(6),e254-e262.
13. Verma, S.,Miles, D.,Gianni, L.,Krop, I. E, Welslau, M.,Baselga, J.,Pegram, M.,Oh, D.Y.,Diéras, V.,Guardino, E.,Fang, L.,Lu, M. W.,Olsen, S.,Blackwell, K.(2012).Trastuzumab emtansine for HER2-positive advanced breast cancer.The New England Journal of Medicine,367(19),1783-1791.
14. 姜紹青(2014)。Ado-trastuzumab emtansine： 第一個用於固態腫瘤之抗體結合藥品。腫瘤護理雜誌，14(2)，19-26。