The therapeutic potential of a novel PSMA antibody and its IL-2 conjugate in prostate cancer

Yoshiyuki Sugimoto, Maiko Hirota, Kazuhiro Yoshikawa, Makoto Sumitomo, Kogenta Nakamura, Ryuzo Ueda, Rinpei Niwa, Toshiyuki Suzawa, Motoo Yamasaki, Kenya Shitara, Takashi Kato, Kazuyasu Nakamura

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13 Citations (Scopus)

Abstract

Prostate-specific membrane antigen (PSMA) is an attractive target for treatment of prostate cancer. Using the PSMA-recognizing mouse monoclonal antibody 2C9 obtained in our previous study, the biological activities of PSMA antibody were evaluated. Mouse-human chimeric IgG1 of 2C9 (KM2777) showed antibody-dependent cellular cytotoxicity activity against PSMA-expressing prostate cancer cells in the presence of human peripheral blood mononuclear cells (PBMCs). To increase lymphocyte-mediated cytotoxicity of KM2777, C-terminus interleukin-2 (IL-2)-fused KM2777 (KM2812) was constructed. KM2812 retained binding activity to PSMA and exhibited growth-stimulating activity equivalent to IL-2 on the IL-2-dependent T-cell line CTLL-2. Moreover, KM2812 exhibited enhanced cytotoxic activity against PSMA-expressing prostate cancer cells in the presence of PBMCs compared with KM2777. In a xenograft tumor model using PSMA-expressing prostate cancer cells, KM2812 exhibited marked antitumor activity, accompanied by complete regression of tumor in some of the KM2812-treated mice. These results suggest that KM2812 has a therapeutic potential for prostate cancer by stimulating lymphocyte-mediated antitumor cytotoxicity.

Original languageEnglish
Pages (from-to)89-97
Number of pages9
JournalAnticancer Research
Volume34
Issue number1
Publication statusPublished - 2014 Jan 1

Keywords

  • Antibodydependent cellular cytotoxicity
  • IL-2
  • Immunocytokine
  • Prostate cancer
  • Prostate-specific membrane antigen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sugimoto, Y., Hirota, M., Yoshikawa, K., Sumitomo, M., Nakamura, K., Ueda, R., Niwa, R., Suzawa, T., Yamasaki, M., Shitara, K., Kato, T., & Nakamura, K. (2014). The therapeutic potential of a novel PSMA antibody and its IL-2 conjugate in prostate cancer. Anticancer Research, 34(1), 89-97.