Pulsed Photothermal Therapy of Solid Tumors as a Precondition for Immunotherapy
Negin Farivar, Nastaran Khazamipour, Morgan E. Roberts, Irina Nelepcu, Mona Marzban, Alireza Moeen, Htoo Zarni Oo, Nader Al Nakouzi, Casper Dolleris, Peter C. Black, Mads Daugaard
Abstract
Photothermal therapy (PTT) refers to the use of plasmonic nanoparticles to convert electromagnetic radiation in the near infrared region to heat and kill tumor cells. Continuous wave lasers have been used clinically to induce PTT, but the treatment is associated with heat-induced tissue damage that limits usability. Here, 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 are reported. Long-pulsed PTT induces acute necrotic cell death in heat affected areas and the release of tumor associated antigens. This antigen release triggers maturation and stimulation of CD80/CD86 in dendritic cells in vivo that primes a cytotoxic T cell response. Accordingly, long-pulsed PTT enhances the therapeutic effects of immune checkpoint inhibition and increases survival of mice with bladder cancer. Combined, the data promote long-pulsed PTT as a safe and effective strategy for enhancing therapeutic responses to immune checkpoint inhibitors while minimizing unwanted tissue damage.