Cancer Research on Prevention and Treatment    2022, Vol. 49 Issue (08) : 855-860     DOI: 10.3971/j.issn.1000-8578.2022.21.1466
Research Progress of Antibody-drug Conjugates in Advanced Non-small Cell Lung Cancer
CHEN Yarui1, WANG Jiangtao1, GUAN Quanlin2, JI Wei1, JIAO Fuzhi1
1. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China; 2. Department of Oncology Surgery, First Hospital of Lanzhou University, Lanzhou 730000, China
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Abstract Although targeted, immune and other therapeutic strategies have become the first-line standard therapy for patients with advanced lung cancer, acquired drug resistance is still inevitable in most cases. The advent of antibody-drug conjugates (ADC) provides a new choice. ADC is a new anticancer drug formed by the coupling of targeted anti-tumor monoclonal antibodies and cytotoxic drugs. Compared with chemotherapeutic drugs, ADC has the advantages of high tolerance, accurate target recognition and little effect on non-cancer cells, and has shown good clinical benefits in the treatment of a variety of malignant tumors. This article reviews the application of ADC in advanced non-small cell lung cancer.
Keywords Non-small cell lung cancer      Antibody-drug conjugates      Targeted therapy     
ZTFLH:  R734.2  
Fund:Key Research Program of Gansu Province (No. 2017YFC0908302)
Issue Date: 12 August 2022
 Cite this article:   
CHEN Yarui,WANG Jiangtao,GUAN Quanlin, et al. Research Progress of Antibody-drug Conjugates in Advanced Non-small Cell Lung Cancer[J]. Cancer Research on Prevention and Treatment, 2022, 49(08): 855-860.
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CHEN Yarui
WANG Jiangtao
GUAN Quanlin
JI Wei
JIAO Fuzhi
[1] Herbst RS, Morgensztern D, Boshoff C. The biology and
management of non-small cell lung cancer[J]. Nature, 2018,
553(7689): 446-454.
[2] Socinski MA, Jotte RM, Federico C, et al. Atezolizumab for First-
Line Treatment of Metastatic Nonsquamous NSCLC[J]. N Engl J
Med, 2018, 378(24): 2288-2301.
[3] Luis PA, Ciuleanu TE, Cobo M, et al. First-line nivolumab
plus ipilimumab combinedwith two cycles of chemotherapy in
patients with non-small-cell lung cancer (CheckMate 9LA): an
international, randomised, open-label, phase3 trial[J]. Lancet
Oncol, 2021, 22(2): 198-211.
[4] K?hler G, Milstein C. Continuous cultures of fused cells secreting
antibody of predefined specificity[J]. J Immunol, 2005, 174(5):
[5] Makawita S, Meric-Bernstam F. Antibody-Drug Conjugates:
Patient and Treatment Selection[J]. Am Soc Clin Oncol Educ
Book, 2020: 40: 1-10.
[6] Leung D, Wurst JM, Liu T, et al. Antibody Conjugates-Recent
Advances and Future Innovations[J]. Antibodies (Basel), 2020:
9(1): 2.
[7] Goulet DR, Atkins WM. Considerations for the Design of Antibody-
BasedTherapeutics[J]. J Pharm Sci, 2019, 109(1): 74-103.
[8] Chau A, Steeg PS, Figg WD. Antibody-drug conjugates for
cancer[J]. Lancet, 2019, 394(10200): 793-804.
[9] Schumacher D, Helma J, Schneider A, et al. Chemical
functionalization strategies and intracellular applications of
nanobodies[J]. Angew Chem Int Ed Engl, 2018, 57(9): 2314-2333.
[10] Mccombs JR, Owen SC. Antibody Drug Conjugates: Design
and Selection of Linker, Payload and Conjugation Chemistry[J].
AAPS J, 2015, 17(2): 339-351.
[11] Dan N, Setua S, Kashyap VK, et al. Antibody-Drug Conjugates
for Cancer Therapy: Chemistry to Clinical Implications[J].
Pharmaceuticals (Basel), 2018, 11(2): 32.
[12] Beck A, Goetsch L, Dumontet C, et al. Strategies and challenges
for thenext generation of antibody-drug conjugates[J]. Nat Rev
Drug Discov, 2017, 16(5): 315-337.
[13] Elgersma RC, Coumans RGE, Huijbregts T, et al. Design,
Synthesis, andEvaluation of Linker-Duocarmycin Payloads:
Toward Selection of HER2-Targeting Antibody-Drug Conjugate
SYD985[J]. Mol Pharma, 2015, 12(6): 1813-1835.
[14] Sutherland MSK, Walter RB, Jeffrey SC, et al. SGN-CD33A:
a novel CD33-targeting antibody-drug conjugate using a
pyrrolobenzodiazepine dimer is active in models of drug-resistant
AML[J]. Blood, 2013, 122(8): 1455-1463.
[15] Olivier Jr KJ, Hurvitz SA. Antibody-Drug Conjugates:
Fundamentals, Drug, Development, and Clinical Outcomes to
Target Cancer[M]. Wiley, 2016.
[16] Robichaux JP, Elamin YY, Vijayan RSK, et al. Pan-Cancer
Landscape and Analysis of ERBB2 Mutations Identifies
Poziotinib as a Clinically Active Inhibitor and Enhancer of T-DM1
Activity[J]. Cancer Cell, 2020, 37(3): 420.
[17] Li BT, Michelini F, Misale S, et al. HER2-mediated internalization
of cytotoxic agents in ERBB2 amplified or mutant lung cancers[J].
Cancer Discov, 2020, 10(5): 674-687.
[18] Lewis Phillips GD, Li G, Dugger DL, et al. Targeting
HER2-positive breast cancer with trastuzumab-DM1, an
antibodyecytotoxic drug conjugate[J]. Cancer Res, 2008, 68(22):
[19] Li BT, Michelini F, Misale S, et al. HER2-Mediated Internalization
of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung
Cancers[J]. Cancer Dis Covery, 2020, 10(5): 674-687.
[20] Pommier Y. Topoisomerase I inhibitors: camptothecins and
beyond[J]. Nat Rev Cancer, 2006, 6(10): 789-802.
[21] Andrikopoulou A, Zografos E, Liontos M, et al. Trastuzumab
deruxtecan(DS-8201a): the latest research and advances in breast
cancer[J]. Clin Breast Cancer, 2021, 21(3): e212-e219.
[22] Tsurutani J, Iwata H, Krop I, et al. Targeting HER2 with
trastuzumab deruxtecan: a dose-expansion, Phase I Study in
multiple advanced solid tumors[J]. Cancer Discov, 2020, 10(5):
[23] Smit EF, Nakagawa K, Nagasaka M, et al. Trastuzumab deruxtecan
(T-DXd; DS-8201) in patients with HER2-mutated metastatic nonsmall
cell lung cancer (NSCLC): Interim results of DESTINYLung01[
J]. J Clin Oncol, 2020, 38(15_suppl): 9504-9504.
[24] Nakagawa K, Nagasaka M, Felip E, et al. OA04.05 Trastuzumab
Deruxtecan in HER2-Overexpressing Metastatic Non-Small Cell
Lung Cancer: InterimResults of DESTINY-Lung01[J]. J Thoracic
Oncol, 2021, 16(3): 28-31.
[25] Liu Y, Lian W, Zhao X, et al. SKB264 ADC: A first-in-human
study of SKB264 in patients with locally advanced unresectable/
metastatic solid tumors who are refractory to available standard
therapies[J]. J Clin Oncol, 2020, 38(15_suppl): TPS3659-
[26] Hamilton EP, Barve MA, Bardia A, et al. Phase 1 dose escalation
of XMT-1522, a novel HER2-targeting antibody-drug conjugate
(ADC), in patients (pts) with HER2-expressing breast, lung and
gastric tumors[J]. J Clin Oncol, 2018, 36(15_suppl): 2546-2546.
[27] Goldenberg DM, Stein R, Sharkey RM. The emergence of
trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer
target[J]. Oncotarget, 2018,9(48): 28989-29006.
[28] Goldenberg DM, Cardillo TM, Govindan SV, et al. Trop-2 is a
novel target for solid cancer therapy with sacituzumab govitecan
(IMMU-132), anantibody-drug-conjugate(ADC)[J]. Oncotarget,
2015, 6(26): 22496-22512.
[29] Jiang A, Gao X, Zhang D, et al. Expression and clinical
significance of the Trop-2 gene in advanced non-small cell lung
carcinoma[J]. Oncol Lett, 2013, 6(2): 375-380.
[30] Bardia A, Messersmith WA, Kio EA, et al. Sacituzumab
Govitecan, a Trop-2-Directed Antibody-Drug Conjugate, for
Patients with Epithelial Cancer:Final Safety and Efficacy Results
from the Phase 1/2 IMMU-132-01 Basket Trial[J]. Ann Oncol,

2021, 32(16): 746-756.

[31] Heist RS, Guarino MJ, s G, et al. Therapy of advanced nonsmall-
cell lung cancer with an SN-38-anti-T rop-2 drug conjugate,
sacituzumab govitecan[J]. J Clin Oncol, 2017, 35(24): 2790-2797.
[32] Meric-Bernstam F, Spira AI. TROPION-Pan Tumor 01: Dose
analysis ofThe TROP2-directed antibody-drug conjugate (ADC)
datopotamab deruxtecan (Dato-DXd, DS-1062) for the treatment
(Tx) of advanced or metastatic non-small cell lung cancer
(NSCLC)[J]. J Clin Oncol, 2021, 39(15): 9058.
[33] Ko B, He T, Gadgeel S, et al. MET/HGF pathway activation as a
paradigm of resistance to targeted therapies[J]. Ann Transl Med,
2017, 5(1): 4.
[34] Salgia R. MET in Lung Cancer: Biomarker Selection Based on
Scientific Rationale[J]. Mol Cancer Ther, 2017, 16(4): 555-565.
[35] Wang J, Anderson MG, Oleksijew A, et al. ABBV-399, a c-Met
Antibody Drug Conjugate that Targets Both MET Amplified and
c-Met OverexpressingTumors, Irrespective of MET Pathway
Dependence[J]. Clin Cancer Res, 2016, 23(4): 992-1000.
[36] Goldman J, Angevin E, Strickler J, et al. MA 02.10 Phase I Study
of ABBV-399 (Telisotuzumab Vedotin) as Monotherapy and in
Combination with Erlotinib in NSCLC[J]. J Thoracic Oncol,
2017, 12(11): 1805-1806.
[37] Strickler JH, Weekes CD, Nemunaitis J, et al. First-in-human
phaseⅠ, dose-escalation and expansion study of telisotuzumab
vedotin, an antibody-drug conjugate targeting c-Met, in patients
with advanced solid tumors[J]. J Clin Oncol, 2018, 36(33):
[38] Waqar SN, Redman MW, Arnold SM, et al. A phase Ⅱ study of
telisotuzumab vedotin in patients with c-MET-positive stage Ⅳ
or recurrent squamous cell lung cancer (LUNG-MAP Sub-study
S1400K, NCT03574753)[J]. Clin Lung Cancer, 2020, 22(3):
[39] Kawakami H, Yonesaka K. HER3 and its ligand, heregulin, as
targets forcancer therapy[J]. Recent Pat Anticancer Drug Discov,
2016, 11(3): 267-274.
[40] Yonesaka K, Hirotani K, Kawakami H, et al. Anti-HER3
monoclonal antibody patritumab sensitizes refractory non-small
cell lung cancer to the epidermal growth factor receptor inhibitor
erlotinib[J]. Oncogene, 2016, 35(7): 878-886.
[41] Watanabe S, Yonesaka K, Tanizaki J, et al. Targeting of the
HER2/HER3signaling axis overcomes ligand-mediated resistance
to trastuzumab in HER2-positive breast cancer[J]. Cancer Med,
2019, 8(3): 1258-1268.
[42] 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[J]. Clin Cancer Res, 2019, 25(23): 7151-7161.
[43] Yu HA, Baik CS, Gold K, et al. LBA62 Efficacy and safety
of patritumab deruxtecan (U3-1402), a novel HER3 directed
antibody drug conjugate, in patients (pts) with EGFR-mutated
(EGFRm) NSCLC-Science Direct[J]. Ann Oncol, 2020, 31:
[44] Yonesaka K, Takegawa N, Watanabe S, et al. An HER3-targeting
antibody-drug conjugate incorporating a DNA topoisomerase
I inhibitor U3-1402 conquers EGFR tyrosine-kinase-inhibitorresistantNSCLC[
J]. Oncogene, 2019, 9(38): 1398-1409.
[45] Haratani K, Yonesaka K, Takamura S, et al. U3-1402 sensitizes
HER3-expressing tumors to PD-1 blockade by immune
activation[J]. J Clin Invest, 2020, 130(1): 374-388.
[46] Jiang Z, Hao Y, Ding X, et al. The effects and mechanisms of
SLC34A2on tumorigenicity in human non-small cell lung cancer
stem cells[J]. Tumor Biol, 2016, 37(8): 10383-10392.
[47] Heynemann S, Yu H, Churilov L, et al. NaPi2b expr‍ession in a
large surgical Non-Small Cell Lung Cancer (NSCLC) cohort[J].
Clin Lung Cancer, 2022, 23(2): e90-e98.
[48] Bodyak ND, Mosher R, Yurkovetskiy AV, et al. The dolaflexinbased
antibody-drug conjugate XMT-1536 targets the solid tumor
lineage antigen SLC34A2/NaPi2b[J]. Mol Cancer Ther, 2021,
20(5): 896-905.
[49] Richardson DL, Barve MA, Strauss JF, et al. PhaseⅠ expansion
studyof XMT-1536, a novel NaPi2b-targeting antibody-drug
conjugate (ADC): preliminary efficacy, safety, and biomarker
results in patients with previously treatedmetastatic ovarian cancer
(OC) or non-small cell lung cancer (NSCLC)[J]. Clin Oncol,
2020, 38(15_suppl): 3549.
[50] Kato S, Okamura R, Mareboina M, et al. Revisiting Epidermal
Growth Factor Receptor ( EGFR) Amplification as a Target for
Anti-EGFR Therapy: Analysis of Cell-Free Circulating Tumor
DNA in Patients With Advanced Malignancies[J]. JCO Precis
Oncol, 2019, 3: PO.18.00180.
[51] Ramalingam SS, Vansteenkiste J, Planchard D, et al. Overall
survival with osimertinib in untreated, EGFR-mutated advanced
NSCLC[J]. N Engl J Med, 2020, 382(1): 41-50.
[52] Xu RH, Qiu MZ, Zhang Y, et al. First-in-human dose-escalation
study ofanti-EGFR ADC MRG003 in patients with relapsed/
refractory solid tumors[J]. Clin Oncol, 2020, 38(15_suppl): 3550.
[53] Jang S, Powderly JD, Spira AI, et al. Phase 1 dose escalation study
of MGC018, an anti-B7-H3 antibody-drug conjugate (ADC)
in patients with advanced solid tumors[J]. Clin Oncol, 2021,
39(15_suppl): 2631-2632.
[54] Radovich M, Solzak JP, Hancock BA, et al. Abstract PS10-26:
An initialsafety study of gedatolisib plus cofetuzumab pelidotin
for metastatic triple-negative breast cancer[J]. Cancer Res, 2021,
81(4): 10-26.
[55] Gébleux R, Stringhini M, Casanova R, et al. Non-internalizing
antibody-drug conjugates display potent anti-cancer activity
upon proteolytic release of monomethyl auristatin E in the
subendothelial extracellular matrix[J].Int J Cancer, 2017, 140(7):
[56]Whalen KA, White BH, Quinn JM, et al. Targeting the
Somatostatin Receptor 2 with the Miniaturized Drug Conjugate,
PEN-221: A Potent and Novel Therapeutic for the Treatment
of Small Cell Lung Cancer[J]. Mol Cancer Ther, 2019, 18(11):

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