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In vivo therapeutic effect of CDH3/P-cadherin-targeting radioimmunotherapy

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Abstract

Purpose

We examined the possible efficacy of the yttrium-90 (90Y)-labeled anti-CDH3/P-cadherin mouse monoclonal antibody (MAb-6) in radioimmunotherapy (RIT) for lung and colorectal cancers that express CDH3/P-cadherin.

Experimental design

MAb-6 was established using genetic immunization. The biodistribution of MAb-6 in nude mice with lung and colorectal cancers was examined by administering indium-111(111In)-labeled MAb-6 to mice. The mice were prepared by inoculation of CDH3/P-cadherin-positive (EBC1, H1373, and SW948) and CDH3/P-cadherin-negative (A549 and RKO) tumor cells. Therapeutic effects and toxicity were investigated by administration of 90Y-labeled MAb-6 (90Y-MAb-6) to EBC, H1373, and SW948-inoculated mice.

Results

Our in vivo results confirmed the specific binding of MAb-6 to tumor cells after intravenous injections of 111In-labeled MAb-6 to mice with tumors expressing CDH3/P-cadherin. A single intravenous injection of 90Y-MAb-6 (100 μCi) significantly suppressed tumor growth in mice with tumors expressing CDH3/P-cadherin. Furthermore, two injections of 90Y-MAb-6 led to complete tumor regression in H1373-inoculated mice without any detectable toxicity.

Conclusions

Our findings demonstrate that CDH3/P-cadherin-targeting RIT with 90Y-MAb-6 is a promising strategy for the treatment for cancers expressing CDH3/P-cadherin.

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Acknowledgments

We would like to thank Dr. Megumi Takayanagi for contributions to this project. This study was funded by Oncotherapy Science Inc.

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Diagnosis of Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Hiroki Yoshioka, Shinji Yamamoto, Pramila Paudyal, Tetsuya Higuchi, Hideyuki Tominaga, Noboru Oriuchi & Keigo Endo

  2. Oncotherapy Science Inc., Kanagawa Science Park R&D D6F, 3-2-1 Sakado, Takatsu-ku, Kawasaki, Kanagawa, 213-0012, Japan

    Hiroki Yoshioka, Shinji Yamamoto, Yasuhiro Shiba, Koji Yoshida, Ryuji Osawa, Toyomasa Katagiri & Takuya Tsunoda

  3. Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Hirofumi Hanaoka, Yasuhiko Iida & Keigo Endo

  4. Laboratory of Biomarker Development, Center for Genomic Medicine, RIKEN, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-0071, Japan

    Hidewaki Nakagawa

  5. Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cyou, Tokushima, 770-8503, Japan

    Toyomasa Katagiri

  6. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Yusuke Nakamura

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  1. Hiroki Yoshioka
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  2. Shinji Yamamoto
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  3. Hirofumi Hanaoka
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  7. Hideyuki Tominaga
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  8. Noboru Oriuchi
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  14. Takuya Tsunoda
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Corresponding author

Correspondence to Hiroki Yoshioka.

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Yoshioka, H., Yamamoto, S., Hanaoka, H. et al. In vivo therapeutic effect of CDH3/P-cadherin-targeting radioimmunotherapy. Cancer Immunol Immunother 61, 1211–1220 (2012). https://doi.org/10.1007/s00262-011-1186-0

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  • DOI: https://doi.org/10.1007/s00262-011-1186-0

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