Combination Photothermal Therapy and αCD137 Agonistic Co-stimulation as a Therapy for SM1 Melanoma
Open AccessThe goal of this dissertation was to evaluate the efficacy and the biological outcomes of combining photothermal therapy and αCD137 co-stimulatory therapy using citrate Prussian Blue nanoparticles in a single nanoparticle construct. Photothermal therapy is an emerging therapy that uses lasers and photothermal agents to destroy tumors with heat ablation. While many investigations have shown promise, photothermal therapy does not provide secondary stimuli to maintain a robust antitumor immune response. αCD137 co-stimulatory therapy was halted in clinical trials due to the hepatotoxicity it elicited at effective doses. While co-administration of αCD137 has been previously explored, concomitant delivery of PTT and αCD137 with a single nanoparticle has not. Furthermore, the electrostatic binding of αCD137 to Prussian Blue nanoparticles (αCD137-PBNPs) and injecting them directly into the tumor microenvironment offers the potential for hepatotoxic mitigation. The work in this dissertation focused on optimizing the synthesis of αCD137-PBNPs, verifying their photothermal and agonistic function, and evaluating the efficacy of PTT on in vivo survival. It was found that αCD137 optimally coats Prussian Blue at a ratio of 2mg Prussian Blue to 1mg αCD137 and that this coating has no major effects on the photothermal properties of Prussian Blue or the agonistic function of αCD137 even after PTT. PTT with αCD137-PBNPs elicited a simultaneous immunostimulatory and immunosuppressive response from SM1 melanoma. Finally, αCD137-PBNPs elicited survival and resistance to tumor rechallenge in 50% of the mice treated. This dissertation highlights the therapeutic potential of αCD137-PBNPs as a concomitant therapy.
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