Redefining photodynamic therapy beyond local : Nanoparticle-enabled photodynamic-immune stimulation for treatment of hot and cold cancers

Résumé :

Photodynamic therapy (PDT) is a cancer-treatment modality that, under the appropriate treatment parameters, can induce immunogenic tumor cell death and stimulate anti-tumor immunity (photodynamic immune stimulation, PDIS). This has the potential to prime adaptive immune responses capable of targeting distant, untreated lesions, as well as eradicating primary treated tumor. The clinical impact of PDT has been limited by conventional photosensitizers, which often exhibit poor tumor selectivity and insufficient immune activation. Nanomedicine-based photosensitizer platforms offer a promising strategy to overcome such limitations. Porphysomes (PS), a class of all-organic, multifunctional porphyrin-lipid nanoparticles currently in Phase I clinical trials for positron emission tomography (PET) imaging of metastatic gynecological cancers, represent one such platform.

This seminar will focus on our work investigating PS-PDIS to drive systemic anti-tumor immunity across tumor models of different immunogenicity, including immunologically “hot” colorectal (CT26) tumors and “cold” melanoma (B16F10) and ovarian (ID8) tumors. The findings establish a strategy to expand PDT beyond localized tumor ablation toward systemic disease control, including prevention of recurrence and metastasis in cold tumors typically resistant to conventional immunotherapies. The seminar will also highlight ongoing efforts to develop gold nanocluster-based platforms for both light- and radiation-mediated immune stimulation in pancreatic cancer, further expanding the scope of nanomaterial-enabled photodynamic and radiodynamic immune stimulation.

This work was supported by the Terry Fox Research Institute (PPG 1137) and the Government of Canada’s New Frontiers in Research Fund (NFRF) (#NFRFT-2020-00573). »

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Contact : anne-laure.bulin@univ-grenoble-alpes.fr