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
N1 - Funding Information:
Funding: This study was supported by the grants from MEXT (KAKENHI 25861140, 17K10497, and 18H02774) and the National Institutes for Quantum and Radiological Science and Technology.
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.
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U2 - 10.3390/ijms19102979
DO - 10.3390/ijms19102979
M3 - Article
C2 - 30274301
AN - SCOPUS:85054078261
VL - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 10
M1 - 2979
ER -