TY - JOUR T1 - The Therapeutic Potential of a Novel PSMA Antibody and its IL-2 Conjugate in Prostate Cancer JF - Anticancer Research JO - Anticancer Res SP - 89 LP - 97 VL - 34 IS - 1 AU - YOSHIYUKI SUGIMOTO AU - MAIKO HIROTA AU - KAZUHIRO YOSHIKAWA AU - MAKOTO SUMITOMO AU - KOGENTA NAKAMURA AU - RYUZO UEDA AU - RINPEI NIWA AU - TOSHIYUKI SUZAWA AU - MOTOO YAMASAKI AU - KENYA SHITARA AU - TAKASHI KATO AU - KAZUYASU NAKAMURA Y1 - 2014/01/01 UR - http://ar.iiarjournals.org/content/34/1/89.abstract N2 - 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. ER -