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

doi:10.3390/ijms19102979

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

International Center for Cell and Gene Therapy

Research output: Contribution to journal › Article › peer-review

18 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 language	English
Article number	2979
Journal	International journal of molecular sciences
Volume	19
Issue number	10
DOIs	https://doi.org/10.3390/ijms19102979
Publication status	Published - 10-2018

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

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Sugyo, A., Tsuji, A. B., Sudo, H., Koizumi, M., Ukai, Y., Kurosawa, G., Kurosawa, Y., Saga, T., & Higashi, T. (2018). 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. International journal of molecular sciences, 19(10), Article 2979. https://doi.org/10.3390/ijms19102979

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title = "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",

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.",

keywords = "Combination therapy, Extracellular matrix metalloproteinase inducer, Gemcitabine, Pancreatic cancer, Radioimmunotherapy",

author = "Aya Sugyo and Tsuji, {Atsushi B.} and Hitomi Sudo and Mitsuru Koizumi and Yoshinori Ukai and Gene Kurosawa and Yoshikazu Kurosawa and Tsuneo Saga and Tatsuya Higashi",

note = "Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2018",

month = oct,

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Sugyo, A, Tsuji, AB, Sudo, H, Koizumi, M, Ukai, Y, Kurosawa, G, Kurosawa, Y, Saga, T & Higashi, T 2018, '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', International journal of molecular sciences, vol. 19, no. 10, 2979. https://doi.org/10.3390/ijms19102979

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. / Sugyo, Aya; Tsuji, Atsushi B.; Sudo, Hitomi et al.
In: International journal of molecular sciences, Vol. 19, No. 10, 2979, 10.2018.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Sugyo, Aya

AU - Tsuji, Atsushi B.

AU - Sudo, Hitomi

AU - Koizumi, Mitsuru

AU - Ukai, Yoshinori

AU - Kurosawa, Gene

AU - Kurosawa, Yoshikazu

AU - Saga, Tsuneo

AU - Higashi, Tatsuya

PY - 2018/10

Y1 - 2018/10

N2 - 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.

AB - 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.

KW - Combination therapy

KW - Extracellular matrix metalloproteinase inducer

KW - Gemcitabine

KW - Pancreatic cancer

KW - Radioimmunotherapy

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Sugyo A, Tsuji AB, Sudo H, Koizumi M, Ukai Y, Kurosawa G et al. 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. International journal of molecular sciences. 2018 Oct;19(10):2979. doi: 10.3390/ijms19102979