BACKGROUND: There is presently no effective therapy for relapsing, metastatic, androgen-independent prostate cancer. Immunotherapy with monoclonal antibody-vehicled toxins (Immunotoxins, ITs) may be a promising novel treatment option for the management of prostate cancer in these cases.METHODS: Three anti-prostate specific membrane antigen (anti-PSMA) monoclonals (J591, PEQ226.5, and PM2P079.1) were cross-linked to ricin A-chain (RTA; native or recombinant), and their cytotoxic effects were investigated in monolayer and three-dimensional (3-D) cell cultures of prostate carcinoma cells (LNCaP).RESULTS: The various Immunotoxins showed effects in the nanomolar range (IC(50s) of 1.6-99 ng/ml) against PSMA+ cells (IC(50) being the concentration inhibiting 50% cell proliferation or protein synthesis). PSMA(-) cell lines were 62- to 277-fold less sensitive to anti-PSMA ITs, evidencing an appreciable therapeutic window. Treatment with J591-smpt-nRTA (0.35-31.7ng/ml) resulted in complete eradication of 3-D tumor micromasses or in 1.46- to 0.35-log reduction of target cells number, depending on the dose.CONCLUSION: Anti-PSMA ITs appear to be promising for use in the eradication of small prostate tumor cell aggregates present in tissues and in the bone marrow.
Anti-tumor effects of toxins targeted to the prostate specific membrane antigen.
Fracasso, G.Conceptualization
;Bellisola, G.;Cingarlini, S.;Castelletti, D.;Tridente, G.;Colombatti, M.
Funding Acquisition
2002-01-01
Abstract
BACKGROUND: There is presently no effective therapy for relapsing, metastatic, androgen-independent prostate cancer. Immunotherapy with monoclonal antibody-vehicled toxins (Immunotoxins, ITs) may be a promising novel treatment option for the management of prostate cancer in these cases.METHODS: Three anti-prostate specific membrane antigen (anti-PSMA) monoclonals (J591, PEQ226.5, and PM2P079.1) were cross-linked to ricin A-chain (RTA; native or recombinant), and their cytotoxic effects were investigated in monolayer and three-dimensional (3-D) cell cultures of prostate carcinoma cells (LNCaP).RESULTS: The various Immunotoxins showed effects in the nanomolar range (IC(50s) of 1.6-99 ng/ml) against PSMA+ cells (IC(50) being the concentration inhibiting 50% cell proliferation or protein synthesis). PSMA(-) cell lines were 62- to 277-fold less sensitive to anti-PSMA ITs, evidencing an appreciable therapeutic window. Treatment with J591-smpt-nRTA (0.35-31.7ng/ml) resulted in complete eradication of 3-D tumor micromasses or in 1.46- to 0.35-log reduction of target cells number, depending on the dose.CONCLUSION: Anti-PSMA ITs appear to be promising for use in the eradication of small prostate tumor cell aggregates present in tissues and in the bone marrow.File | Dimensione | Formato | |
---|---|---|---|
2002_The_Prostate.pdf
accesso aperto
Tipologia:
Versione dell'editore
Licenza:
Dominio pubblico
Dimensione
191.22 kB
Formato
Adobe PDF
|
191.22 kB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.