Targeted systemic therapy of prostate cancer with a monoclonal antibody to prostate-specific membrane antigen☆
Section snippets
Prostate-specific membrane antigen
Prostate-specific membrane antigen (PSMA) is the single most well-established, highly restricted prostate epithelial cell membrane antigen known.2, 3, 4, 5, 6, 7The gene has been cloned, sequenced,3 and mapped to chromosome 11p.8 Although first thought to be entirely prostate-specific,2, 3, 4 subsequent studies demonstrated that PSMA is also expressed by cells of the small intestine, proximal renal tubules, and salivary glands.6 However, the level of expression in these nonprostate tissues is
Monoclonal antibodies to PSMAext
Following our hypothesis, we produced the first series of IgG mAbs to PSMAext (J591, J415, J533, and E99).18 Enzyme-linked immunosorbent assays (ELISAs) confirmed that these mAbs to PSMAext bound to the same molecule as 7E11 but did not compete with 7E11 for binding.18 Immunoprecipitation and Western blot assays confirmed unmistakably that these mAbs bound to the 100-kd PSMA.18 In contrast to 7E11/CYT-356, these mAbs recognize two distinct epitopes located on the exterior of the cell.18, 19
Conclusion
PSMA represents an ideal cell surface protein for targeted therapy of prostate cancer and vasculotoxic therapy of nonprostate solid cancers. Clinical trials using mAb J591, which recognizes the extracellular domain of PSMA, indicate that this antibody can effectively target disseminated prostate and non-prostate cancers in patients. Furthermore, J591 can be used to deliver radioisotopes or other cytotoxins to these cancer sites. Major, objective responses have been seen in the phase I prostate
References (31)
- et al.
Expression of prostate-specific membrane antigen (PSMA) in normal, benign and malignant prostate tissues
Urol Oncol
(1995) - et al.
Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy
Urology
(1996) - et al.
PSMA expression is greatest in prostate adenocarcinoma and lymph node metastases
Urology
(1998) - et al.
Biochemical characterization and mapping of the 7E11-C5.3 epitope of the prostate-specific membrane antigen
Urol Oncol
(1995) - et al.
Structure of membrane glutamate carboxypeptidase
Biochim Biophys Acta
(1997) - et al.
Maytansine
Cancer Treat Rev
(1978) Ligand, targeted therapeutics in anticancer therapy
Nat Rev Cancer
(2002)- et al.
Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients
Anticancer Res
(1987) - et al.
Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen
Cancer Res
(1994) - et al.
Expression of the prostate-specific membrane antigen
Cancer Res
(1994)
Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids
Int J Cancer
A dual-monoclonal sandwich assay for prostate-specific membrane antigenLevels in tissues, seminal fluid and urine
Prostate
Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinomaA study of 184 cases
Cancer
Prostate-specific membrane antigenA novel folate hydrolase in human prostatic carcinoma cells
Clin Cancer Res
111 Indium-capromab pendetide in the evaluation of patients with residual or recurrent prostate cancer after radical prostatectomy
J Urol
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Prostate-specific Membrane Antigen Biology in Lethal Prostate Cancer and its Therapeutic Implications
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2021, Cancer LettersCitation Excerpt :We await more data regarding this combination and biomarker analyses. Prostate specific membrane antigen (PSMA) is a cell surface marker expressed on prostate cancer cells that can be imaged with PET-imaging as well as targeted therapeutically [68,69]. While PSMA PET-imaging was recently approved by the FDA for disease localization for high risk localized and biochemical recurrent prostate cancer, PET-imaging in mCRPC has been performed mainly in the context of clinical trials.
Nuclear imaging for immune cell tracking in vivo – Comparison of various cell labeling methods and their application
2021, Coordination Chemistry ReviewsPSMA-Directed CAR T Cells Combined with Low-Dose Docetaxel Treatment Induce Tumor Regression in a Prostate Cancer Xenograft Model
2020, Molecular Therapy OncolyticsCitation Excerpt :We previously demonstrated that the D7 scFv binds PSMA with high affinity and specificity.15 Moreover, we showed that its parental 3/F11 antibody recognizes a different extracellular epitope in PSMA than J591.15,40 It is therefore interesting to speculate that the high in vitro and in vivo efficacy of D7-based PSMA CAR T cells is based on optimal positioning of the CAR to recognize the target epitope.
Preparation of <sup>177</sup> Lu-Trastuzumab injection for treatment of breast cancer
2019, Applied Radiation and Isotopes
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Supported in part by NIH General Clinical Research Centers Program (NCRR Grant No. M01RR00047); US Department of Army (DAMD17-98-1-8594), Cancer Research Institute, Cap Cure, the David H. Koch Foundation, the Peter Sacerdote Foundation, BZL Biologics, Inc, and Millennium Pharmaceuticals, Inc. N.H.B. developed the J591 antibody used in this study. J591 and related anti-PSMAext antibody patents were assigned to the Cornell Research Foundation and subsequently licensed to BZL Biologics, Inc. N.H.B. is a paid consultant to BZL Biologics, Inc.