Clinical development of antibody-drug conjugates in triple negative breast cancer: can we jump higher?

References

• Bianchini G, Balko JM, Mayer IA, et al. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016 Nov;13(11):674–690.
   PubMed Web of Science ®Google Scholar
• Kassam F, Enright K, Dent R, et al. Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin Breast Cancer. 2009 Feb;9(1):29–33.
   PubMed Web of Science ®Google Scholar
• Pondé NF, Zardavas D, Piccart M. Progress in adjuvant systemic therapy for breast cancer. Nat Rev Clin Oncol. 2019 Jan;16(1):27–44.
   PubMed Web of Science ®Google Scholar
• Zardavas D, Piccart M. Neoadjuvant therapy for breast cancer. Annu Rev Med. 2015 Jan 14;66(1):31–48.
   PubMed Web of Science ®Google Scholar
• Foulkes WD, Smith IE, Reis-Filho JS. Triple-Negative Breast Cancer. N Engl J Med. 2010 Nov 11;363(20):1938–1948.
   PubMed Web of Science ®Google Scholar
• Gonzalez-Angulo AM, Timms KM, Liu S, et al. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res. [2011 Mar 1];17(5):1082–1089.
   PubMed Web of Science ®Google Scholar
• Hartman A-R, Kaldate RR, Sailer LM, et al. Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer. Cancer. [2012 Jun 1];118(11):2787–2795.
   PubMed Web of Science ®Google Scholar
• Wong-Brown MW, Meldrum CJ, Carpenter JE, et al. Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. Breast Cancer Res Treat. 2015 Feb;150(1):71–80.
   PubMed Web of Science ®Google Scholar
• Robson M, S-A I, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a Germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523–533.
   PubMed Web of Science ®Google Scholar
• Litton JK, Rugo HS, Ettl J, et al. Talazoparib in Patients with advanced breast cancer and a Germline BRCA mutation. N Engl J Med. 2018 Aug 23 379(8):753–763.
   PubMed Web of Science ®Google Scholar
• Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018 Nov 29;379(22):2108–2121.
   PubMed Web of Science ®Google Scholar
• Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec;396(10265):1817–1828.
   PubMed Web of Science ®Google Scholar
• Beck A, Goetsch L, Dumontet C, et al. Strategies and challenges for the next generation of antibody–drug conjugates. Nat Rev Drug Discov. 2017 May;16(5):315–337.
   PubMed Web of Science ®Google Scholar
• Zhang A, Fang J, Chou RY-T, et al. Conformational difference in human IgG2 disulfide isoforms revealed by hydrogen/deuterium exchange mass spectrometry. Biochemistry (Mosc). 2015 Mar 17 54(10):1956–1962.
   Web of Science ®Google Scholar
• McCombs JR, Owen SC. Antibody drug conjugates: design and selection of linker, payload and conjugation chemistry. Aaps J. 2015 Mar;17(2):339–351.
   PubMed Web of Science ®Google Scholar
• Gromek S, Balunas M. Natural products as exquisitely potent cytotoxic payloads for antibody- drug conjugates. Curr Top Med Chem. 2015 Jan 5; 14(24):2822–2834.
   PubMed Web of Science ®Google Scholar
• Shen B-Q, Xu K, Liu L, et al. Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates. Nat Biotechnol. 2012 Feb;30(2):184–189.
   PubMed Web of Science ®Google Scholar
• Tsuchikama K, An Z. Antibody-drug conjugates: recent advances in conjugation and linker chemistries. Protein Cell. 2018 Jan;9(1):33–46.
   PubMed Web of Science ®Google Scholar
• Xu S. Internalization, trafficking, intracellular processing and actions of antibody-drug conjugates. Pharm Res. 2015 Nov;32(11):3577–3583.
   PubMed Web of Science ®Google Scholar
• Junttila TT, Li G, Parsons K, et al. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat. 2011 Jul;128(2):347–356.
   PubMed Web of Science ®Google Scholar
• Staudacher AH, Brown MP. Antibody drug conjugates and bystander killing: is antigen-dependent internalisation required? Br J Cancer. 2017 Dec;117(12):1736–1742.
   PubMed Web of Science ®Google Scholar
• Singh AP, Seigel GM, Guo L, et al. Evolution of the systems pharmacokinetics-pharmacodynamics model for antibody-drug conjugates to characterize tumor heterogeneity and in vivo bystander effect. J Pharmacol Exp Ther. 2020 Jul;374(1):184–199.
   PubMed Web of Science ®Google Scholar
• Sayama Y, Kaneko M, Kato Y. Development and characterization of TrMab‑6, a novel anti‑TROP2 monoclonal antibody for antigen detection in breast cancer. Mol Med Rep Internet]. 2020 Nov 25 cited 2021 Nov 1;23(2). Available from
   PubMed Web of Science ®Google Scholar
• Son S, Shin S, Rao NV, et al. Anti-Trop2 antibody-conjugated bioreducible nanoparticles for targeted triple negative breast cancer therapy. Int J Biol Macromol. 2018 Apr;110:406–415.
   PubMed Web of Science ®Google Scholar
• Starodub AN, Ocean AJ, Shah MA, et al. First-in-human trial of a novel anti-trop-2 antibody-SN-38 conjugate, Sacituzumab govitecan, for the treatment of diverse metastatic solid tumors. Clin Cancer Res. 2015 Sep 1 21(17):3870–3878.
   PubMed Web of Science ®Google Scholar
• Bardia A, Mayer IA, Diamond JR, et al. Efficacy and safety of anti-trop-2 antibody drug conjugate Sacituzumab govitecan (IMMU-132) in heavily pretreated patients with metastatic triple-negative breast cancer. J Clin Oncol. [2017 Jul 1];35(19):2141–2148.
   PubMed Web of Science ®Google Scholar
• Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab Govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med. 2019 Feb 21;380(8):741–751.
   PubMed Web of Science ®Google Scholar
• Wahby S, Fashoyin-Aje L, Osgood CL, et al. FDA approval summary: accelerated approval of Sacituzumab govitecan-hziy for third-line treatment of metastatic triple-negative breast cancer. Clin Cancer Res. [2021 Apr 1];27(7):1850–1854.
   PubMed Web of Science ®Google Scholar
• Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021 Apr 22;384(16):1529–1541.
   PubMed Web of Science ®Google Scholar
• Bardia A. LBA4 - Datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate (ADC), for triple-negative breast cancer (TNBC): preliminary results from an ongoing phase 1 trial. Esmo Breast Cancer Virtual Congr. 2021. Mini Oral Sess 2.
   Google Scholar
• Schalper KA, Kumar S, Hui P, et al. A retrospective population-based comparison of HER2 immunohistochemistry and fluorescence in situ hybridization in breast carcinomas: impact of 2007 American society of clinical oncology/college of American pathologists criteria. Arch Pathol Lab Med. 2014 Feb;138(2):213–219.
   PubMed Web of Science ®Google Scholar
• Fehrenbacher L, Cecchini RS, Geyer CE, et al. NSABP B-47/NRG oncology phase III randomized trial comparing adjuvant chemotherapy with or without trastuzumab in high-risk invasive breast cancer negative for HER2 by FISH and with IHC 1+ or 2. J Clin Oncol Off J Am Soc Clin Oncol. [2020 Feb 10];38(5):444–453.
   Google Scholar
• Schettini F, Chic N, Brasó-Maristany F, et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. Npj Breast Cancer. [2021 Jan 4];7(1):1.
   PubMed Web of Science ®Google Scholar
• Modi S, Park H, Murthy RK, et al. Antitumor activity and safety of trastuzumab deruxtecan in patients with HER2-low–expressing advanced breast cancer: results from a phase ib study. J Clin Oncol. 2020 Jun 10;38(17):1887–1896.
   PubMed Web of Science ®Google Scholar
• Modi S, Ohtani S, Lee CC, et al. A phase III, multicenter, randomized, open label trial of [fam-] trastuzumab deruxtecan (DS-8201a) versus investigator’s choice in HER2-low breast cancer. J Clin Oncol. 2019 May 20;37(15_suppl): TPS1102–TPS1102.
   PubMed Web of Science ®Google Scholar
• Schmid P, Nunes AT, Dry H, et al. BEGONIA: phase 1b/2, open-label, platform study of the safety and efficacy of durvalumab (D) ± paclitaxel (P) with novel oncology therapies for first-line metastatic triple-negative breast cancer (mTNBC): addition of arm 7, D + datopotamab deruxtecan (Dato-DXd; DS-1062). J Clin Oncol. [2021 May 20];39(15_suppl): TPS1105–TPS1105.
   Web of Science ®Google Scholar
• Dokter W, Ubink R, van der Lee M, et al. Preclinical profile of the HER2-targeting ADC SYD983/SYD985: introduction of a new duocarmycin-based linker-drug platform. Mol Cancer Ther. 2014 Nov;13(11):2618–2629.
   PubMed Web of Science ®Google Scholar
• Van der Lee MMC, Groothuis PG, Ubink R, et al. the preclinical profile of the duocarmycin-based HER2-targeting ADC SYD985 predicts for clinical benefit in low HER2-expressing breast cancers. Mol Cancer Ther. 2015 Mar;14(3):692–703.
   PubMed Web of Science ®Google Scholar
• Nadal-Serrano M, Morancho B, Escrivá-de-romaní S, et al. The second generation antibody-drug conjugate SYD985 overcomes resistances to T-DM1. Cancers (Basel). [2020 Mar 13];12(3):670.
   Web of Science ®Google Scholar
• Banerji U, van Herpen CML, Saura C, et al. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019 Aug;20(8):1124–1135.
   PubMed Web of Science ®Google Scholar
• Koutras AK, Fountzilas G, Kalogeras KT, et al. The upgraded role of HER3 and HER4 receptors in breast cancer. Crit Rev Oncol Hematol. 2010 May;74(2):73–78.
   PubMed Web of Science ®Google Scholar
• Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009 Jul;9(7):463–475.
   PubMed Web of Science ®Google Scholar
• Holbro T, Beerli RR, Maurer F, et al. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: Erbb2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci. [2003 Jul 22];100(15):8933–8938.
   PubMed Web of Science ®Google Scholar
• Choi B-K, Fan X, Deng H, et al. ERBB3 (HER3) is a key sensor in the regulation of ERBB-mediated signaling in both low and high ERBB2 (HER2) expressing cancer cells. Cancer Med. 2012 Aug;1(1):28–38.
   PubMed Web of Science ®Google Scholar
• Sinevici N, Ataeinia B, Zehnder V, et al., HER3 differentiates basal from claudin type triple negative breast cancer and contributes to drug and microenvironmental induced resistance. Front Oncol. 2020 Nov 20;10:554704.
   PubMed Web of Science ®Google Scholar
• Ogden A, Bhattarai S, Sahoo B, et al. Combined HER3-EGFR score in triple-negative breast cancer provides prognostic and predictive significance superior to individual biomarkers. Sci Rep. 2020 Dec;10(1):3009.
   PubMed Web of Science ®Google Scholar
• Hashimoto Y, Koyama K, Kamai Y, et al. A novel HER3-targeting antibody–drug conjugate, U3-1402, exhibits potent therapeutic efficacy through the delivery of cytotoxic payload by efficient internalization. Clin Cancer Res. [2019 Dec 1];25(23):7151–7161.
   PubMed Web of Science ®Google Scholar
• Krop I, Yonemori K, Takahashi S, et al. Safety and efficacy results from the phase 1/2 study of U3-1402, a human epidermal growth factor receptor 3 (HER3)-directed antibody drug conjugate (ADC), in patients with HER3-expressing metastatic breast cancer (MBC). Cancer Res. 2021;81(4_Supplement):D1–09.
   Web of Science ®Google Scholar
• Manning DL, Daly RJ, Lord PG, et al. Effects of oestrogen on the expression of a 4.4 kb mRNA in the ZR-75-1 human breast cancer cell line. Mol Cell Endocrinol. 1988 Oct;59(3):205–212.
   PubMed Web of Science ®Google Scholar
• Yamashita S, Miyagi C, Fukada T, et al. Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer. Nature. [2004 May 20];429(6989):298–302.
   PubMed Web of Science ®Google Scholar
• Lue H-W, Yang X, Wang R, et al. LIV-1 promotes prostate cancer epithelial-to-mesenchymal transition and metastasis through HB-EGF shedding and EGFR-mediated ERK signaling. Plos One. 2011;6(11):e27720.
   PubMed Web of Science ®Google Scholar
• Hogstrand C, Kille P, Ackland ML, et al. A mechanism for epithelial–mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3). Biochem J. [2013 Oct 15];455(2):229–237.
   PubMed Web of Science ®Google Scholar
• Lopez V, Kelleher SL. Zip6-attenuation promotes epithelial-to-mesenchymal transition in ductal breast tumor (T47D) cells. Exp Cell Res. 2010 Feb 1;316(3):366–375.
   PubMed Web of Science ®Google Scholar
• Manning DL, Robertson JF, Ellis IO, et al. Oestrogen-regulated genes in breast cancer: association of pLIV1 with lymph node involvement. Eur J Cancer Oxf Engl 1990. 1994;30A(5):675–678.
   PubMed Web of Science ®Google Scholar
• Sussman D, Smith LM, Anderson ME, et al. SGN–LIV1A: a novel antibody–drug conjugate targeting LIV-1 for the treatment of metastatic breast cancer. Mol Cancer Ther. 2014 Dec;13(12):2991–3000.
   PubMed Web of Science ®Google Scholar
• Modi S, Pusztai L, Forero A, et al. Abstract PD3-14: phase 1 study of the antibody-drug conjugate SGN-LIV1A in patients with heavily pretreated triple-negative metastatic breast cancer. In: Poster Discussion Abstracts [Internet]. American Association for Cancer Research; 2018 [cited 2021 Jun 22]. p. PD3–14–PD3–14. Available from:
   Google Scholar
• Han H, Diab S, Alemany C, et al. Abstract PD1-06: open label phase 1b/2 study of ladiratuzumab vedotin in combination with pembrolizumab for first-line treatment of patients with unresectable locally-advanced or metastatic triple-negative breast cancer. In: Poster Spotlight Session Abstracts [Internet]. American Association for Cancer Research; 2020 [cited 2021 Jun 22]. p. PD1–06–PD1–06. Available from:
   Google Scholar
• Samanta D, Almo SC. Nectin family of cell-adhesion molecules: structural and molecular aspects of function and specificity. Cell Mol Life Sci. 2015 Feb;72(4):645–658.
   PubMed Web of Science ®Google Scholar
• Takano A, Ishikawa N, Nishino R, et al. Identification of nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer. Cancer Res. [2009 Aug 15];69(16):6694–6703.
   PubMed Web of Science ®Google Scholar
• DeRycke MS, Pambuccian SE, Gilks CB, et al. Nectin 4 overexpression in ovarian cancer tissues and serum: potential role as a serum biomarker. Am J Clin Pathol. 2010 Nov;134(5):835–845.
   PubMed Web of Science ®Google Scholar
• Fabre-Lafay S, Monville F, Garrido-Urbani S, et al. Nectin-4 is a new histological and serological tumor associated marker for breast cancer. BMC Cancer [Internet]. 2007 Dec cited 2021 Dec 1;7(1). Available from.
   PubMed Web of Science ®Google Scholar
• Challita-Eid PM, Satpayev D, Yang P, et al. Enfortumab vedotin antibody–drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res. [2016 May 15];76(10):3003–3013.
   PubMed Web of Science ®Google Scholar
• M-Rabet M, Cabaud O, Josselin E, et al. Nectin-4: a new prognostic biomarker for efficient therapeutic targeting of primary and metastatic triple-negative breast cancer. Ann Oncol. 2017 Apr;28(4):769–776.
   PubMed Web of Science ®Google Scholar
• Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med. [2021 Mar 25];384(12):1125–1135.
   PubMed Web of Science ®Google Scholar
• Bruce JY, Pusztai L, Braiteh F, et al. EV-202: a phase II study of enfortumab vedotin in patients with select previously treated locally advanced or metastatic solid tumors. J Clin Oncol. 2020;38 (15_suppl). doi:https://doi.org/10.1200/JCO.2020.38.15_suppl.TPS3647 .
   Google Scholar
• O’Shannessy DJ, Somers EB, Smale R, et al. Expression of folate receptor-α (FRA) in gynecologic malignancies and its relationship to the tumor type. Int J Gynecol Pathol Off J Int Soc Gynecol Pathol. 2013 May 32(3):258–268.
   PubMed Web of Science ®Google Scholar
• O’Shannessy DJ, Yu G, Smale R, et al. Folate receptor alpha expression in lung cancer: diagnostic and prognostic significance. Oncotarget. 2012 Apr;3(4):414–425.
   PubMedGoogle Scholar
• O’Shannessy DJ, Somers EB, Maltzman J, et al. Folate receptor alpha (FRA) expression in breast cancer: identification of a new molecular subtype and association with triple negative disease. Springerplus. 2012;1:22.
   PubMedGoogle Scholar
• Zhang Z, Wang J, Tacha DE, et al. Folate receptor α associated with triple-negative breast cancer and poor prognosis. Arch Pathol Lab Med. 2014 Jul;138(7):890–895.
   PubMed Web of Science ®Google Scholar
• Cheung A, Opzoomer J, Ilieva KM, et al. Anti-folate receptor alpha-directed antibody therapies restrict the growth of triple-negative breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. [2018 Oct 15];24(20):5098–5111.
   Google Scholar
• Ab O, Whiteman KR, Bartle LM, et al. IMGN853, a folate receptor-α (FRα)-targeting antibody-drug conjugate, exhibits potent targeted antitumor activity against FRα-expressing tumors. Mol Cancer Ther. 2015 Jul;14(7):1605–1613.
   PubMed Web of Science ®Google Scholar
• Moore KN, Oza AM, Colombo N, et al. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757–765.
   PubMed Web of Science ®Google Scholar
• Yam C, Rauch GM, Rahman T, et al. A phase II study of mirvetuximab soravtansine in triple-negative breast cancer. Invest New Drugs. 2021 Apr;39(2):509–515.
   PubMed Web of Science ®Google Scholar
• Cheng X, Li J, Tanaka K, et al. MORAb-202, an antibody-drug conjugate utilizing humanized anti-human FRα farletuzumab and the microtubule-targeting agent eribulin, has potent antitumor activity. Mol Cancer Ther. 2018 Dec;17(12):2665–2675.
   PubMed Web of Science ®Google Scholar
• Furuuchi K, Rybinski K, Fulmer J, et al. Antibody-drug conjugate MORAb-202 exhibits long-lasting antitumor efficacy in TNBC PDx models. Cancer Sci. 2021 Jun;112(6):2467–2480.
   PubMed Web of Science ®Google Scholar
• Shimizu T, Fujiwara Y, Yonemori K, et al. First-in-human phase 1 study of MORAb-202, an antibody–drug conjugate comprising farletuzumab linked to eribulin mesylate, in patients with folate receptor-α–positive advanced solid tumors. Clin Cancer Res. 2021;27(14) :3905–3915.
   PubMed Web of Science ®Google Scholar
• Zardavas D, Baselga J, Piccart M. Emerging targeted agents in metastatic breast cancer. Nat Rev Clin Oncol. 2013 Apr;10(4):191–210.
   PubMed Web of Science ®Google Scholar
• Williams M, Spreafico A, Vashisht K, et al. Patient selection strategies to maximize therapeutic index of antibody–drug conjugates: prior approaches and future directions. Mol Cancer Ther. 2020 Sep;19(9):1770–1783.
   PubMed Web of Science ®Google Scholar
• Kim YH, Tavallaee M, Sundram U, et al. Phase II investigator-initiated study of brentuximab vedotin in mycosis fungoides and Sézary syndrome with variable CD30 expression level: a multi-institution collaborative project. J Clin Oncol Off J Am Soc Clin Oncol. [2015 Nov 10];33(32):3750–3758.
   Google Scholar
• Gerber H-P, Sapra P, Loganzo F, et al. Combining antibody–drug conjugates and immune-mediated cancer therapy: what to expect? Biochem Pharmacol. 2016;102:1–6.
   PubMed Web of Science ®Google Scholar
• Iwata TN, Sugihara K, Wada T, et al. [Fam-] trastuzumab deruxtecan (DS-8201a)-induced antitumor immunity is facilitated by the anti–CTLA-4 antibody in a mouse model. Najbauer J editor. Plos One 2019 Oct 1;14(10):e0222280.
   PubMed Web of Science ®Google Scholar
• McKenzie JA, Mbofung RM, Malu S, et al. The effect of topoisomerase I inhibitors on the efficacy of T-cell-based cancer immunotherapy. Jnci J Natl Cancer Inst. [2018 Jul 1];110(7):777–786.
   Web of Science ®Google Scholar
• Barok M, Joensuu H, Isola J. Trastuzumab emtansine: mechanisms of action and drug resistance. Breast Cancer Res. 2014 Apr;16(2):3378.
   Web of Science ®Google Scholar
• Loganzo F, Tan X, Sung M, et al. Tumor cells chronically treated with a trastuzumab-maytansinoid antibody-drug conjugate develop varied resistance mechanisms but respond to alternate treatments. Mol Cancer Ther. 2015 Apr;14(4):952–963.
   PubMed Web of Science ®Google Scholar
• Chang C-H, Wang Y, Zalath M, et al. Combining ABCG2 inhibitors with IMMU-132, an anti–trop-2 antibody conjugate of SN-38, overcomes resistance to SN-38 in breast and gastric cancers. Mol Cancer Ther. 2016 Aug;15(8):1910–1919.
   PubMed Web of Science ®Google Scholar
• Drago JZ, Modi S, Chandarlapaty S. Unlocking the potential of antibody–drug conjugates for cancer therapy. Nat Rev Clin Oncol. 2021 Jun;18(6):327–344.
   PubMed Web of Science ®Google Scholar
• Blanco B, Domínguez-Alonso C, Alvarez-Vallina L. Bispecific immunomodulatory antibodies for cancer immunotherapy. Clin Cancer Res. 2021;27(20): :5457–5464. doi:https://doi.org/10.1158/1078-0432.CCR-20-3770.
   PubMed Web of Science ®Google Scholar
• Schuster SJ. Bispecific antibodies for the treatment of lymphomas: promises and challenges. Hematol Oncol. 2021 Jun;39(S1):113–116.
   PubMed Web of Science ®Google Scholar
• Li JY, Perry SR, Muniz-Medina V, et al. A biparatopic HER2-targeting antibody-drug conjugate induces tumor regression in primary models refractory to or ineligible for HER2-targeted therapy. Cancer Cell. 2016 Jan;29(1):117–129.
   PubMed Web of Science ®Google Scholar
• Hamblett K, Barnscher S, Davies R, et al. Abstract P6-17-13: ZW49, a HER2 targeted biparatopic antibody drug conjugate for the treatment of HER2 expressing cancers. In: Poster Session Abstracts [Internet]. American Association for Cancer Research; 2019 [cited 2021 Jul 6]. p. P6–17–13–P6–17–13. Available from:
   Google Scholar