Research Highlight


A patient with a tumor in the left inguinal lymph node, near the spine. After being imaged via PET/CT, the separate PET and CT images are combined to generate a single PET/CT (bottom) image, which measures the location and metabolic activity within tumors in one setting.

Longitudinal assessment of tumor heterogeneity during immunotherapy for metastatic melanoma

Melanoma is an aggressive form of skin cancer that develops from genetic changes in melanocytes, the pigment producing cells in the epidermal layers of skin. Traditional treatments for melanoma include surgery, radiation therapy, and systemic therapy. Patients with early stages of melanoma have a 90% survival rate over 5 years in the United States. However, patients with advanced melanoma, where the tumor has metastasized to other parts of the body, only have a 10% survival rate over 5 years and less than 25% of patients survive for longer than 1 year. Thus, novel targeted treatment approaches like immunotherapy are being investigated in medical research and clinical trials to improve the survival rates of patients with metastatic melanoma. In this investigation, patients with metastatic melanoma were treated with a novel immunotherapeutic agent and the metabolic activity of their tumors was measured using Positron Emission Tomography Computed Tomography (PET/CT) imaging, before, during and after the induction dose of the immunotherapy. PET/CT was used to measure changes in tumor characteristics (e.g. size and metabolic activity) during the course of the therapy. These patients were also monitored after the end of therapy to evaluate their clinical outcome (e.g. remission, progression, or recurrence of their disease) and survival rates. The PET/CT images of these patients will be analyzed to assess how the tumor characteristics changed in response to the immunotherapy, and to observe variations or heterogeneity. The heterogeneity of metabolic activity within and between the tumors in the same patient, and in the cohort of patients will be measured during this analysis. The immunotherapeutic agent was a monoclonal antibody that targets cytotoxic T-lymphocyte antigen-4 (CTLA-4), a protein receptor found on the surface of activated T cells. CTLA-4 acts as a brake for the immune system. When CTLA-4 binds to ligands on the surface of melanoma cells, it downregulates the activation of T cells and prevents the immune system from destroying the tumors. The monoclonal antibody specifically binds to CTLA-4 and inhibits the function of the bound protein molecule, thus boosting the immune system’s response to the tumors. Oncologists routinely use imaging throughout traditional treatment to observe the effects of treatment and determine the next course of action. When melanoma cells are killed by the immune system during immunotherapy, changes in the characteristics of the metastatic tumors may be observed with PET/CT imaging, which provides two complementary components of tumor characterization that are important for monitoring the cytotoxic effect of immunotherapy. PET measures metabolic activity within tumor cells with high sensitivity but has limited spatial resolution, while CT provides high resolution anatomical imaging but cannot differentiate between active and dead tumor tissue. Therefore, combined PET/CT imaging measures location and metabolic activity within tumors in one setting. For PET/CT imaging, patients were injected with the glucose analog 18F-fluorodeoxyglucose (18F-FDG) to measure metabolic activity of their tumors. As a glucose analog, 18F-FDG is transported into cells that require glucose as an energy source. Cancer cells tend to use more glucose than cells in the surrounding tissue (the Warburg effect), so tumors uptake more 18F-FDG and appear as hyperintense regions in PET/CT images. When the 18F undergoes nuclear decay, it emits a positron, a positively-charged particle with the mass of an electron. Emitted positrons travel a very short distance before interacting with an electron and annihilating, releasing two gamma rays that travel in opposite directions. PET detects these pairs of annihilation gamma rays and pinpoints the location and quantity of 18F-FDG within the tumor and surrounding tissues, while CT provides the anatomical reference for the location of the detected 18F-FDG signals.

 

 


Trainee Research

CaNCURE provides trainees with a 6-month hands-on research experience and one-on-one mentoring by leading researchers in cancer nanomedicine.   Projects performed by current and past participants include:

Nano-plasmonic exosome (nPLEX) assays for exosome analysis and antibody validation

Radiotherapeutic synergism of thermogelling cisplatin-loaded polymers for cervical cancer treatment

Targeting CXCR4/SDF-1a using phytochemicals to inhibit progression and metastasis of pancreatic cancer

Co-delivery of antibiotics and topoisomerase inhibitors to overcome chemoresistance

The Assessment and Comparison of Ferumoxtran as Contrast Imaging Agent in Patients with Pancreatic Cancers.

Development of PSMA-targeting nanoparticles for positron emitting tomography imaging in prostate cancer using animal models

miRNA analysis in mouse model of metastatic breast cancer. (Proj 2) The inhibition of PD-L1 on a Pan02 cell line w/ siRNA-nanodrug & gemcitabine treatment

Nanoencapsulation of tyrosine kinase inhibitors and their effects on pathway inhibition

Quantitative Multimodal Imaging of Tumor Response to Radiation

Small T Antigen Effect on Mitotic Proteins B-Myb and FOXM1

Investigating the use of Feraheme to monitor the immune response by PET in general inflammation and specific immune cell populations

Online monitoring and image-guided treatment of chemoresistant micrometastases

Optimization of macrophage-targeted nanoparticles for positron emission tomography imaging in cancer

Development of Smart INCeRT Brachytherapy Spacers via PLGA and Docetaxel for Combined Chemo-Radiation Therapies in Prostate Cancer

Localized chemo- and chemo-radiation for the treatment of prostate cancer

Clinical immunotherapy application in metastatic glioblastoma

Co-delivery of protective substrate and chemotherapy drugs via lipid Bilayer Mesoporous Silica Nanoparticles

Combined delivery of targeted liposomal chemotherapeutics and photodynamic therapy to treat pancreatic cancer

Surface-targeting, ligand-switching nanoparticles for mitochondrial drug delivery in prostate cancer

Investigating the use of iron chelator deferoxamine (DFO)-bearing PEG-like nanoprobes as a multifunctional agent for cancer therapy and PET imaging

Iron-chelating PEG-like nanoprobes as therapeutic and 89Zr/PET imaging agents

Assessing the reproducibility of MRI-based brain tumor measurements between both observers and MRI vendors

Erythropoietin improves antitumor immune response through reversal of the hypoxic tumor microenvironment

Pharmacokinetic analysis of changes in temozolomide distribution after antiangiogenic treatment of glioblastoma

Biological mechanisms of gold nanoparticle-enhanced radiation therapy of prostate cancer


Soleil Doggett (Biology, '16) talks to her fellow peers about her research on oxygenating tumors to stimulate the anti-tumor immune response.

 


Trainee e-portfolios

Photo credit: Tom Kates Photography

While on co-op, trainees document their research in an e-portfolio.  This gives trainees the opportunity to provide regular updates on their research progress, reflect on training they are receiving, and explain how their research fits within the field of cancer nanomedicine.  These research e-portfolios can be accessed through individual trainee profiles.  The complete collection may be found here.

Check out this month’s featured e-portfolios by Rachel Fontana and Jordan Harris!

 


Presentation at CaNCURE Nanomedicine Day

At the completion of their co-op, trainees are provided with the opportunity to present their research to a wider audience.  In our 1st annual CaNCURE Nanomedicine Day, trainees prepared interactive, digital posters to display on electronic poster boards.  Over 100 faculty, students, and researchers attended our first event!

Check out the news article and congrats to all the poster winners!

Jordan Harris: Most Innovative Cancer Research Award
Jeremy Thong: Best Undergraduate Research Poster Award
Craig Pille: Most Promising Translational Research Award
Bryan Kynnap: Most Promising Basic Science Award
Jordan Harris: Top Chemical Engineering Poster Award