Efficacy evaluation of combination treatment using gemcitabine and radioimmunotherapy with90 y-labeled fully human anti-CD147 monoclonal antibody 059-053 in a BxPC-3 xenograft mouse model of refractory pancreatic cancer

Aya Sugyo, Atsushi B. Tsuji, Hitomi Sudo, Mitsuru Koizumi, Yoshinori Ukai, Gene Kurosawa, Yoshikazu Kurosawa, Tsuneo Saga, Tatsuya Higashi

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6 Citations (Scopus)

Abstract

The poor prognosis of pancreatic cancer requires the development of more effective therapy. CD147 expresses in pancreatic cancer with high incidence and has a crucial role in invasion and metastasis. We developed a fully human monoclonal antibody (059-053) with high affinity for CD147. Here we evaluated the efficacy of combined treatment using radioimmunotherapy (RIT) with90 Y-labeled 059-053 and gemcitabine in a BxPC-3 xenograft mouse model. Expression of CD147 and matrix metalloproteinase-2 (MMP2) in BxPC-3 tumors was evaluated. In vitro and in vivo properties of 059-053 were evaluated using111 In-labeled 059-053 and a pancreatic cancer model BxPC-3. Tumor volume and body weight were periodically measured in mice receiving gemcitabine, RIT, and both RIT and gemcitabine (one cycle and two cycles). High expression of CD147 and MMP2 was observed in BxPC-3 tumors and suppressed by 059-053 injection. Radiolabeled 059-053 bound specifically to BxPC-3 cells and accumulated highly in BxPC-3 tumors but low in major organs. Combined treatment using RIT with gemcitabine (one cycle) significantly suppressed tumor growth and prolonged survival with tolerable toxicity. The two-cycle regimen had the highest anti-tumor effect, but was not tolerable. Combined treatment with90 Y-labeled 059-053 and gemcitabine is a promising therapeutic option for pancreatic cancer.

Original languageEnglish
Article number2979
JournalInternational journal of molecular sciences
Volume19
Issue number10
DOIs
Publication statusPublished - 10-2018

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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