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抗體-藥物偶聯(lián)物（ADC）通過(guò)穩(wěn)定的連接體將細(xì)胞毒性小分子化學(xué)藥物連接到單抗上，使用單抗作為載體將小分子化學(xué)藥物運(yùn)輸?shù)侥繕?biāo)腫瘤細(xì)胞，利用靶抗原介導(dǎo)的細(xì)胞內(nèi)吞作用使ADC進(jìn)入腫瘤內(nèi)部，之后釋放出小分子藥物從而達(dá)到殺死腫瘤細(xì)胞的目的[1]。為新輔助治療后非pCR的HER2陽(yáng)性患者帶來(lái)希望的T-DM1就是具有代表性的ADC，同時(shí)也是首個(gè)在中國(guó)獲批的ADC。 T-DM1使用曲妥珠單抗（T）作為載體，將微管抑制藥物DM1（美坦新衍生物）靶向遞送到HER2性腫瘤細(xì)胞，他具有兩大特點(diǎn)： 曲妥珠單抗本身就具有抗腫瘤活性，而目前其他獲批的ADC所用的抗體基本只作為藥物的載體，單獨(dú)抗腫瘤效果非常有限[2] DM1的抗腫瘤效價(jià)百倍于普通化療藥物[3-5] T-DM1具有優(yōu)秀的ADC機(jī)制: 
T-DM1單藥用于HER2陽(yáng)性I期乳腺癌輔助治療也顯示出良好的效果，ATEMPT研究初步報(bào)告顯示3年無(wú)疾病生存率為97.7%（曲妥珠單抗聯(lián)合紫杉醇組為92.8%），3年無(wú)復(fù)發(fā)間期率為99.1%[11]。 另一在乳腺癌領(lǐng)域取得重大研發(fā)突破的ADC為DS-8201。DESTINY-Breast01研究發(fā)現(xiàn)，患者無(wú)疾病生存期達(dá)16.4個(gè)月，緩解持續(xù)時(shí)間14.8個(gè)月[12]?；谠摻Y(jié)果，DS-8201在美國(guó)獲得加速批準(zhǔn)，用于既往針對(duì)轉(zhuǎn)移性疾病接受過(guò)≥2線以抗HER2為基礎(chǔ)的方案的不可切除或轉(zhuǎn)移性HER2陽(yáng)性乳腺癌，但該適應(yīng)證在全球其他地區(qū)尚未獲批。戰(zhàn)“疫”當(dāng)前，T-DM1與您攜手共進(jìn)。 1. 抗體偶聯(lián)藥物質(zhì)量控制和臨床前評(píng)價(jià)專(zhuān)家共識(shí).中國(guó)藥事, 2018, 32(7): 991-1004.2. Birrer M J, Moore K N, Betella I, et al. Antibody-drug conjugate-based therapeutics: State of the Science. J Natl Cancer Inst. 2019,111(6):538-549.3. 王彥明,郝伯鈞,李靜,等. 美登素類(lèi)抗體藥物偶聯(lián)物研究進(jìn)展.國(guó)際藥學(xué)研究雜志，2016,43(3): 410-419.4. Barok M, Tanner M, K?ninki K, Isola J. Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Cancer Lett 2011; 306 (2):171-179.5. Junttila TT, Li G, Parsons K, et al. Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer. Breast Cancer Res Treat 2011; 128 (2):347–3566. Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014 ,15(6):640-7.7. Shao Z, Pang D, Yang H, et al. Abstract P6-17-17: Pertuzumab, trastuzumab, and docetaxel for HER2-positive early or locally advanced breast cancer in the neoadjuvant setting: Efficacy and safety analysis of a randomized phase III study in Asian patients (PEONY). Cancer Research 2019,79(4 Supplement):P6-17-17.8. Gianni L, Pienkowski T, Im YH, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016,17(6):791-800.9. van Ramshorst MS, van der Voort A, van Werkhoven ED, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018;19(12):1630-1640.10. von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019,380(7):617-628.11. Tolaney SM, Hu J, Dang C, et al. TBCRC 033: A randomized phase II study of adjuvant trastuzumab emtansine (T-DM1) vs paclitaxel (T) in combination with trastuzumab (H) for stage I HER2-positive breast cancer (BC) (ATEMPT). Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14; San Antonio, TX. Abstract GS1-05.12. Modi S, Saura C, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020;382(7):610-621.
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