The therapeutic potential of a novel PSMA antibody and its IL-2 conjugate in prostate cancer.
Anticancer Res
; 34(1): 89-97, 2014 Jan.
Article
en En
| MEDLINE
| ID: mdl-24403448
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.
Palabras clave
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Glicoproteínas de Membrana
/
Interleucina-2
/
Citotoxicidad Inmunológica
/
Glutamato Carboxipeptidasa II
/
Anticuerpos Monoclonales
/
Antígenos de Superficie
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Anticancer Res
Año:
2014
Tipo del documento:
Article
País de afiliación:
Japón