Comparative analysis of prostate‐specific membrane antigen (PSMA) versus a prostate‐specific membrane antigen‐like gene

  title={Comparative analysis of prostate‐specific membrane antigen (PSMA) versus a prostate‐specific membrane antigen‐like gene},
  author={Denise S. O’Keefe and Dean Bacich and Warren D. W. Heston},
  journal={The Prostate},
Currently prostate‐specific membrane antigen (PSMA) is showing promise both as an imaging and therapeutic target for occult prostate cancer metastases. First generation antibodies against PSMA are used for the FDA approved Prostascint™ monoclonal antibody scan and second generation antibodies are being developed for therapeutic targeting as well as imaging 1 . However, there have been reports describing PSMA expression in non‐prostatic tissues including kidney, liver, and brain. As we had… 

Targeting the prostate-specific membrane antigen for prostate cancer therapy.

The proposed strategies include targeted toxins and radiotherapeutics as well as immunotherapeutic agents and vaccines to treat prostate cancer.

Understanding Prostate-Specific Membrane Antigen and Its Implication in Prostate Cancer

Prostate-specific membrane antigen (PSMA) is a novel marker that represents an excellent ideal cell-surface-bound protein for targeted therapy of prostate cancer and vasculotoxic therapy of

Antibody-drug conjugates targeting prostate-specific membrane antigen.

The preclinical and clinical findings have largely substantiated the promise of PSMA as an ADC target and potential future directions for ADCs that target PSMA are summarized.

Targeting prostate cancer: Prostate‐specific membrane antigen based diagnosis and therapy

The archetypal expression profile of PSMA may be exploited for the treatment with alpha emitters to break radioresistance and thus to bring the power of systemic therapy to higher levels.

Biology of PSMA As a Diagnostic and Therapeutic Target

Second-generation antibodies have been developed that are either genetically engineered humanized antibodies or are fully human antibodies that recognize the extracellular portion of the PSMA protein.

Novel Monoclonal Antibodies Recognizing Human Prostate‐Specific Membrane Antigen (PSMA) as Research and Theranostic Tools

The detailed characterization of four novel murine monoclonal antibodies recognizing human PSMA as well as PSMA orthologs from different species is reported.

Inhibitors of prostate-specific membrane antigen in the diagnosis and therapy of metastatic prostate cancer – a review of patent literature

Most PSMA-targeted agents are based on the Lys-UREa-Glu or Glu-urea-glu structure, demonstrate strong PSMA -binding affinity in nanomolar range, and achieve diverse structural modifications in the non-pharmacophore pocket.

Novel prostate acid phosphatase‐based peptide vaccination strategy induces antigen‐specific T‐cell responses and limits tumour growth in mice

When immunised in a DNA vector format (ImmunoBody®), PAP‐114‐128 prevents and reduces the growth of transgenic adenocarcinoma of mouse prostate‐C1 prostate cancer cell‐derived tumours in both prophylactic and therapeutic settings.

Dual-Target Binding Ligands with Modulated Pharmacokinetics for Endoradiotherapy of Prostate Cancer

RPS-027 shows dual targeting to PSMA and albumin, resulting in a high tumor uptake, highly favorable tissue distribution, and promising therapeutic profile in a preclinical model of prostate cancer.



Prostate‐specific suicide gene therapy using the prostate‐specific membrane antigen promoter and enhancer

An analysis of the PSMA enhancer for the most active region(s) is described and a way of using the enhancer in combination with the E. coli cytosine deaminase gene for suicide‐driven gene therapy that converts the nontoxic prodrug 5‐fluorocytosine into the cytotoxic drug 5‐ fluorouracil in prostate cancer cells.

Prostate-specific membrane antigen is produced in tumor-associated neovasculature.

These findings expand the possible therapeutic role of PSMA and establish it as a unique biomarker specifically produced and expressed by tumor-associated neovasculature but not produced or expressed by normal vessels.

A unique folate hydrolase, prostate-specific membrane antigen (PSMA): a target for immunotherapy?

This review discusses the historical background, biochemical characteristics, gene regulation, potential for targeting, tissue localization, and a novel T-body strategy of prostate-specific membrane antigen.

Prostate-specific membrane antigen expression in normal and malignant human tissues.

The decrease in PSMA immunoreactivity noted in advanced prostate cancer suggests that expression of this molecule may be linked to the degree of tumor differentiation and the neoexpression of PSMA in endothelial cells of capillary beds in certain tumors may be related to tumor angiogenesis and suggests a potential mechanism for specific targeting of tumor neovasculature.

Follow‐up evaluation of a phase II prostate cancer vaccine trial

A phase II trial, involving infusions of autologous dendritic cells (DC) and two human histocompatibility antigen (HLA‐A2)‐specific prostate‐specific membrane antigen (PSMA) peptides, was recently completed and the follow‐up evaluation of 19 responders is described.

Enhanced expression of prostate-specific membrane antigen gene in prostate cancer as revealed by in situ hybridization.

Results clearly show that expression of PSM-specific transcripts is closely associated with malignant transformation of the prostate; thus, in situ hybridization for detection of the transcripts is useful for the diagnosis of prostate cancer.

Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium.

Competitive binding studies indicate these antibodies define two distinct, noncompeting epitopes on the extracellular domain of PSMA, which should prove useful for in vivo targeting to prostate cancer, as well as to the vascular compartment of a wide variety of carcinomas.