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Anti-tumor effects of toxins targeted to the prostate specific membrane antigen.
- Source :
-
The Prostate [Prostate] 2002 Sep 15; Vol. 53 (1), pp. 9-23. - Publication Year :
- 2002
-
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.<br />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).<br />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.<br />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.<br /> (Copyright 2002 Wiley-Liss, Inc.)
- Subjects :
- Antibodies, Monoclonal therapeutic use
Bone Neoplasms secondary
Carboxypeptidases immunology
Glutamate Carboxypeptidase II
Humans
Immunotoxins immunology
Male
Ricin administration & dosage
Tumor Cells, Cultured
Antigens, Surface
Carboxypeptidases pharmacology
Carcinoma pathology
Immunotoxins pharmacology
Prostatic Neoplasms pathology
Ricin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0270-4137
- Volume :
- 53
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Prostate
- Publication Type :
- Academic Journal
- Accession number :
- 12210476
- Full Text :
- https://doi.org/10.1002/pros.10117