PSMA-based Molecular-genetic Reporter System
JHU REF: C12881
Invention Novelty: A method of using the prostate-specific membrane antigen (PSMA) in combination with molecular reporting systems as an expression system to deliver the PSMA gene for diagnosis and imaging of prostate cancer.
Value Proposition:
PSMA is ideally suited to becoming a reporter because it is a human, transmembrane protein that has a restricted expression pattern (primarily in prostate), which will limit background signal, and there are several PSMA imaging agents available for clinical and pre-clinical applications. Current molecular imaging approaches with reporter genes suffer from lack of biocompatibility due to immunogenicity, and from relatively low sensitivity due to widely expression of a reporter throughout normal tissues endogenously or incapability of reliably sequestering the imaging agent within the cell in a high-affinity interaction. PSMA is a human transmembrane protein that possesses many properties that are desirable as a reporter for an imaging system. Its other advantages include:
- The expression of PSMA is limited to the prostate, the proximal tubules of the kidney, and the brain which will limit background signal.
- PSMA expression is low and isolated in healthy tissues, allowing imaging of cells that express the surface form of PSMA at high levels, such as metastatic prostate tumors.
- The combination of tissue-restricted expression, human biocompatibility, available probe diversity, and proven clinical utility support the potential for PSMA as an imaging reporter.
- Sensitive, multimodal non-invasive imaging to monitor and evaluate a population of cells including human cancers.
Technical Details:
PSMA is internalized upon the binding of certain ligands, providing a mechanism to accumulate PSMA-targeting agents within cells. The expression of PSMA is limited to the prostate, the proximal tubules of the kidney, and the brain. Alternative processing results in both cell surface and cytoplasmic isoforms, the latter of which is primarily expressed in the healthy prostate.
The present invention involves in 1) the generation of adenoviral expression particles that express PSMA under the control of CMV promoter, 2) in vitro and in vivo validation of PSMA as an imaging reporter and comparison with two clinically established reporters, the mutant herpes simplex virus type I thymidine kinase (HSV1-tk) and human sodium-iodide symporter (hNIS), 3) the generation of non-viral, episomal vector for systemic delivery and expression of PSMA (full-length and various truncations) under the control of the tumor-specific promoter, 4) in vitro validation of the PSMA episomal vectors as imaging reporters.
Looking for Partners: To license this technology
Stage of Development: Discovery
Data Availability: CDA/NDA
Patent Status: None
Publication(s)/Associated Cases: WO 2015/143029; PMC4074907; C10538
Categories: Prostate Cancer Diagnostics
Keywords: PSMA imaging reporter; Adenoviral expression; HSV-sr39tk and hNIS
