Anti-glypican-1 antibody-drug conjugate is a potential therapy against pancreatic cancer.

British Journal of Cancer
Takahiko NishigakiTetsuji Naka

Abstract

Pancreatic cancer (PDAC) is the most lethal malignancy. New treatment options for it are urgently required. The aim was to develop an antibody-drug conjugate (ADC) targeting glypican-1 (GPC-1) as a new therapy for PDAC. We evaluated GPC-1 expression in resected PDAC specimens and PDAC cell lines. We then measured the antitumour effect of anti-GPC-1 monoclonal antibody conjugated with the cytotoxic agent monomethyl auristatin F (MMAF) in vitro and in vivo. GPC-1 was overexpressed in most primary PDAC cells and tissues. The PDAC cell lines BxPC-3 and T3M-4 strongly expressed GPC-1 relative to SUIT-2 cells. Compared with control ADC, GPC-1-ADC showed a potent antitumour effect against BxPC-3 and T3M-4, but little activity against SUIT-2 cells. In the xenograft and patient-derived tumour models, GPC-1-ADC significantly and potently inhibited tumour growth in a dose-dependent manner. GPC-1-ADC-mediated G2/M-phase cell cycle arrest was detected in the tumour tissues of GPC-1-ADC-treated mice relative to those of control-ADC-treated mice. GPC-1-ADC showed significant tumour growth inhibition against GPC-1-positive pancreatic cell lines and patient-derived, GPC-1-positive pancreatic cancer tissues. Our preclinical data demonstrated tha...Continue Reading

References

May 29, 2008·Genome Biology·Jorge FilmusJonathan Rast
Sep 24, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ezogelin OflazogluHans-Peter Gerber
Dec 22, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Howard A BurrisJoyce A O'Shaughnessy
May 13, 2011·The New England Journal of Medicine·Thierry ConroyUNKNOWN PRODIGE Intergroup
Oct 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jessica KatzAnas Younes
Oct 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Patricia M LoRussoMark X Sliwkowski
Mar 29, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anas YounesRobert Chen
Jun 26, 2012·International Journal of Cancer. Journal International Du Cancer·Takuhei YokoyamaTetsuji Naka
Oct 10, 2012·Annual Review of Medicine·Eric L Sievers, Peter D Senter
Oct 2, 2013·The Lancet Oncology·Werner HartwigMarkus W Büchler
Oct 18, 2013·The New England Journal of Medicine·Daniel D Von HoffMarkus F Renschler
Nov 22, 2015·Pharmacological Reviews·Paul Polakis
Jan 9, 2016·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
May 8, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michinori OguraDavid MacDonald
Oct 22, 2017·International Journal of Cancer. Journal International Du Cancer·Satoko MatsuzakiTetsuji Naka
Oct 25, 2017·British Journal of Cancer·Alexander H Staudacher, Michael P Brown
Dec 24, 2018·The New England Journal of Medicine·Thierry ConroyUNKNOWN Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group

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Citations

Jul 7, 2020·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Nan LiMitchell Ho
Sep 23, 2020·Cardiovascular Engineering and Technology·Sheldon WeinbaumJohn M Tarbell
Oct 4, 2020·Journal of Hematology & Oncology·Yunzhen QianChen Liu
Aug 22, 2020·American Journal of Obstetrics and Gynecology·Ruriko NakaeTadashi Kimura
Jul 13, 2021·Frontiers in Oncology·Simone Furini, Chiara Falciani
Aug 10, 2021·OncoTargets and Therapy·Fatemah O F O AlshammariHamzeh Mohammad Alrawashdeh
Sep 23, 2021·American Journal of Physiology. Cell Physiology·Jiajia Pan, Mitchell Ho

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Methods Mentioned

BETA
biopsy
FACS
transfection
fluorescence-activated
reverse transcription-PCR
Reverse
PCR
xenograft
Flow cytometry
Flow

Software Mentioned

JMP
FlowJo

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