TARGETED RADIOTHERAPY OF CANCER
Auger Electron and Beta Particle Radioimmunotherapy of Breast Cancer. The aim of this research is to discover and evaluate potent radioimmunotherapeutic agents for treatment of HER2-positive breast cancer that is resistant to trastuzumab (Herceptin). These agents consist of monoclonal antibodies or bispecific radioimmunoconjugates modified with metal-chelating polymers that permit radiolabeling to high specific activity with the Auger electron-emitter, 111In or the beta particle emitters, 177Lu or 64Cu. This is a collaboration with Professor Mitch Winnik in the Department of Chemistry at the University of Toronto. In the case of 111In, the targeting agents are further modified with nuclear translocation sequence (NLS) peptides to route the radioimmunoconjugates to the nucleus of breast cancer cells, where the nanometer-micrometer range Auger electrons are most damaging to DNA and lethal. We are currently conducting translational bridge studies to advance one promising agent, 111In-NLS-trastuzumab to Phase I clinical trial in the next 3 years in collaboration with the Ontario Clinical Oncology Group (OCOG). LMIR Researcher: Conrad Chan.
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Radiolabeled Gold Nanoparticles for Treatment of Breast Cancer. The aim of this research is to design and evaluate HER2 and EGFR-targeted gold nanoparticles modified with metal-chelating polymers for complexing the Auger electron emitter, 111In or the beta-particle emitter, 177Lu ("gold nanobombs") for local treatment of breast cancer. These gold nanobombs are being investigated as a novel form of brachytherapy for locally advanced breast cancer (LABC) which often expresses HER2 or EGFR. Patients with LABC have a worse prognosis compared to earlier stages of breast cancer which are confined locally to the breast. We are also planning to extend this approach to systemic treatment of metastatic breast cancer which is triple-negative using the EGFR-targeted gold nanobombs. This is a collaboration with Dr. Jean-Philippe Pignol, a radiation oncologist at Erasmus Medical Centre in Rotterdam, the Netherlands. LMIR Researcher: Zhongli Cai.
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Targeted Polymeric Nanotechnology for Multi-Modality Treatment of HER2-Positive Breast Cancer.
This is a collaborative research project with Professor Christine Allen which aims to design and evaluate block copolymer micelles (BCMs) for combined targeted radiotherapy and chemotherapy of trastuzumab-resistant breast cancer. The BCMs will be modified on their surface with monoclonal antibodies targeting HER2 or EGFR and will incorporate the Auger electron emitter, 111In or the beta emitter, 177Lu as well as chemotherapeutic agents for multi-modality treatment. |