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Farivar, Negin

University of British Columbia

Photothermal therapy (PTT) refers to the use of photothermal agents (plasmonic nanoparticles) to convert electromagnetic radiation in the near infrared region (NIR) to heat and kill the target (tumor) cells. Due to the high efficacy and minimal side effects, this therapy has been studied extensively in recent years and gained significant clinical traction. In addition to cell death, PTT can be used to induce mild hyperthermia in temperatures between 39-45°C, which can trigger certain physiological responses like immune stimulation and cytokine secretion. This immune response can be reinforced in combination with cancer immunotherapies such as immune checkpoint blockade. Although research has demonstrated that pulsed lasers generate more localized heating than continuous wave (CW) lasers, PTT is traditionally administered by CW lasers, and there is a limited amount of research employing pulsed laser equipment. Using the conventional low power CW laser settings requires long treatment times, induces unwanted heat damage to the surrounding healthy tissue, and leads to higher pain sensation in patients; all limiting parameters in clinical translation of PTT. I hypothesized that a novel pulsed laser device could produce a photothermal effect sufficient to stimulate immune cells within the tumor microenvironment and potentially augment the effectiveness of immune checkpoint blockade therapy. Here, we report the engineering and validation of a novel long pulsed laser device able to induce selective and localized mild hyperthermia in tumors while reducing the heat affected zone and unwanted damage to surrounding tissue. Long-pulsed PTT induces acute necrotic cell death in heat affected areas and the release of tumor associated antigens. This antigen release is immunostimulatory and triggers maturation and stimulation of CD80/CD86 in dendritic cells in vivo. In vivo antitumor studies in a MB49 syngeneic bladder cancer model led to significantly reduced tumor growth and increased survival indicating long-pulse PTT can be an effective and promising strategy to enhanced therapeutic responses when combined with anti-PD-L1 immune checkpoint inhibitors.

Text

2024-05-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/84772

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/