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

    Research output: Contribution to journalArticle

    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

    Fingerprint

    Interleukin-2
    Prostatic Neoplasms
    Antibodies
    Blood Cells
    Therapeutics
    Lymphocytes
    Heterografts
    human glutamate carboxypeptidase II
    Neoplasms
    Immunoglobulin G
    Monoclonal Antibodies
    T-Lymphocytes
    Cell Line
    Growth

    Keywords

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

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Sugimoto, Y., Hirota, M., Yoshikawa, K., Sumitomo, M., Nakamura, K., Ueda, R., ... 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.

    The therapeutic potential of a novel PSMA antibody and its IL-2 conjugate in prostate cancer. / Sugimoto, Yoshiyuki; Hirota, Maiko; Yoshikawa, Kazuhiro; Sumitomo, Makoto; Nakamura, Kogenta; Ueda, Ryuzo; Niwa, Rinpei; Suzawa, Toshiyuki; Yamasaki, Motoo; Shitara, Kenya; Kato, Takashi; Nakamura, Kazuyasu.

    In: Anticancer Research, Vol. 34, No. 1, 01.01.2014, p. 89-97.

    Research output: Contribution to journalArticle

    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, vol. 34, no. 1, pp. 89-97.
    Sugimoto Y, Hirota M, Yoshikawa K, Sumitomo M, Nakamura K, Ueda R et al. The therapeutic potential of a novel PSMA antibody and its IL-2 conjugate in prostate cancer. Anticancer Research. 2014 Jan 1;34(1):89-97.
    Sugimoto, Yoshiyuki ; Hirota, Maiko ; Yoshikawa, Kazuhiro ; Sumitomo, Makoto ; Nakamura, Kogenta ; Ueda, Ryuzo ; Niwa, Rinpei ; Suzawa, Toshiyuki ; Yamasaki, Motoo ; Shitara, Kenya ; Kato, Takashi ; Nakamura, Kazuyasu. / The therapeutic potential of a novel PSMA antibody and its IL-2 conjugate in prostate cancer. In: Anticancer Research. 2014 ; Vol. 34, No. 1. pp. 89-97.
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