Developmental Therapeutics (DT)

Select Recent Accomplishments

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Multi-parametric analysis of gene expression, genomic profiling and Androgen Receptor (AR) protein from CTCs. (Gene expression data is shown as a heat map, where red indicates high expression, green low expression, and gray no detectable expression). AR protein analysis of CTCs is shown as a graph of AR nuclear localization verses AR intensity. Sequencing coverage and known oncogenic short variants detected using Foundation One genomic profiling shown with corresponding copy number plots (Clin Cancer Res 201657).

In addition to cell free DNA, circulating tumor cell (CTC) analysis permits frequent, minimally invasive sampling of tumor cells for molecular assessment. An example of Aim 2 research being applied to clinical trials is being conducted by Lang, a DOD Physician Research Training Award  recipient, in collaboration with Beebe (TM). They have optimized a microfluidic technology known as the VERSA (Vertical Exclusion-based Rare Sample Analysis) that integrates capture and analysis of rare tumor cells for protein, gene expression, and genomic information. VERSA utilizes a unique separation principle that enables multiple purification processes in sequence (e.g., cell capture, extracellular staining, nucleic acid extraction) for sequential extraction of multiple analytes from a single sample.

Cancer Immunotherapy

DNA vaccines represent a cost-effective approach to induce antigen-specific immunity. The McNeel lab has advanced a DNA vaccine against human Prostatic Acid Phosphatase (PAP) and the Androgen-Receptor (AR) Ligand-Binding Domain (LBD) into clinical trials. With funding from the NIH/NCI and a DOD Prostate Cancer Research Program Clinical Trial Award, a Phase I and II dose- and schedule-evaluation trial was completed in patients with PSA-recurrent prostate cancer demonstrating that DNA immunization could safely elicit antigen-specific T-cell responses.

Quantitative Total Bone Imaging

Quantitative Total Bone Imaging (QTBI) uses 18F sodium-fluoride (NaF) PET/CT to automatically identify, segment, and characterize osteoblastic lesions in bone using a variety of imaging features. QTBI allows the ability to co-register multiple scans, using an articulated registration strategy, allowing quantification of individual lesions as they change over time providing both spatial and temporal information. This information allows us to perform PET-directed, CT-guided biopsies in both responding and non-responding lesions allowing each patient to serve as his own control (ongoing clinical trial NCT02677376; PIs: Liu and Jeraj (IR)). This capability also allows us to measure change in total functional burden of disease over time and interlesional response heterogeneity, both of which provide novel clinical trial endpoints to optimize dose, combinations, and sequence of therapies. This tool also serves our discovery initiatives as biopsies of resistant lesions can be readily performed to identify new resistance mechanisms and drug targets.
Quantitative Total Bone Imaging (QTBI) is a robust methodology developed by Jeraj and Liu to allow total and inter-lesional assessment of treatment response in osseous metastases. Their multi-center trial (UWCCC, Karmanos, and Rutgers) “A Positron Emission Tomography/Computed Tomography Bone Imaging Study in Patients Receiving Enzalutamide for Castration-Resistant Prostate Cancer”  is ongoing. The purpose of this study is to prospectively evaluate the role of NaF PET/CT as a treatment response biomarker in mCRPC to bone.