Dr. Raymond Reilly

Abstract

Our group has developed a nanoparticle depot (NPD) composed of a small calcium alginate seed that encapsulates gold nanoparticles (AuNPs) loaded with ¹⁹⁸Au. ¹⁹⁸Au-NPD may be inserted into tumours for local radiation treatment (brachytherapy) exploiting the 6 mm range b-particles emitted by ¹⁹⁸Au. Further, ¹⁹⁸Au-NPD irradiation of tumours may cause immunogenic cell death (ICD) that activates cytotoxic T-cells that seek out and attack a distant untreated tumour, extending the range and therapeutic benefit of the ¹⁹⁸Au-NPD. This abscopal (“out-of-the-scope”) immune-mediated effect of radiation may be amplified when combined with immunotherapeutic agents that block immune checkpoints (e.g. PD1-PDL-1) that prevent T-cell recognition of tumour cells. In this presentation, I will describe our studies of ¹⁹⁸Au-NPD alone or combined with anti-PD-L1 immunotherapy in immunocompetent mouse models of TNBC. These include Balb/c mice with 4T1 murine mammary carcinoma tumours and humanized NCG mice that display human T-cells engrafted with MDA-MB-231 human TNBC tumours. The effectiveness of the ¹⁹⁸Au-NPD for local tumour treatment and the abscopal effect on a distant tumour will be discussed. Normal tissue toxicity and tumour and normal organ dosimetry will be presented. Finally, I will propose a multimodal approach that combines ¹⁹⁸Au-NPD with immunotherapy, chemotherapy and Auger electron radioimmunotherapy with ¹¹¹In-labeled anti-epidermal growth factor receptor (EGFR) panitumumab to improve the treatment of primary tumours in the breast and prevent metastatic progression in patients with early-stage TNBC.

Supported by the Canadian Cancer Society and the Canadian Institutes of Health Research.