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NIH Research Festival

September 12 – 14, 2018

Glypican 3-Specific Antibody-Drug Conjugate for Hepatocellular Carcinoma Treatment

Friday, September 14, 2018 – Poster Session V
12:00 – 1:30 p.m.

FAES Terrace

NCI

MOLBIO-8

Authors

  • Y Fu
  • M Ho

Abstract

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Therapeutic outcomes of HCC remain unsatisfactory, and novel treatments are urgently needed. GPC3 is a potential target for HCC given the findings that: 1) GPC3 has been reported to be highly expressed in more than 70% of HCC; 2) elevated GPC3 expression is linked with poor HCC prognosis; 3) GPC3-specific therapeutics including immunotoxin and chimeric antigen receptor T-cells (CART) have shown promising results. We postulate that GPC3 is a potential therapeutic target of antibody-drug conjugates (ADCs) against HCC. To determine the payload for ADCs against liver cancer, we screened three libraries of drugs (>9000 compounds) against three HCC cell lines, and found that the most potent drugs are DNA damaging agents. Duocarmycin SA and pyrrolobenzodiazepine (PBD) dimer were chosen as the payloads to construct GPC3-specific ADCs: hYP7-DC and hYP7-PC. Both ADCs showed potency at picomolar concentrations against a panel of GPC3-positive cancer cell lines, but not GPC3 negative cell lines. To improve the potency, we investigated the synergetic effect of hYP7-DC with approved drugs. Gemcitabine showed a synergetic effect with hYP7-DC in vitro and in vivo. Furthermore, single treatment of hYP7-PC induced tumor regression in different mouse models. Conclusions: our findings support clinical testing of this novel therapeutic candidate in patients with GPC3-positive HCC.

Scientific Focus Area: Molecular Biology and Biochemistry

This page was last updated on Friday, March 26, 2021

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2018 program

Download the 2018 Research Festival Schedule Overview (6 pages)

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Current Research Festival

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  • 2024
    • General Schedule of Events
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    • Special Wednesday Events
    • Vendor Exhibit Information
    • Green Labs Fair
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  • 2023
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    • NIH Early–Career Investigator Lectures
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  • 2021
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    • General Schedule of Events
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    • Data Blitz
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    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
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  • 2018
    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
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    • FARE Award Ceremony
    • Special Exhibits on Resources for Intramural Research
    • Technical Sales Association (TSA) Research Festival Exhibit Tent Show
    • Research Festival Committees
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    • General Schedule of Events
    • Plenary Sessions
    • Concurrent Symposia Sessions
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    • FARE Award Ceremony
    • Future Research Leaders
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