Abstract 7266: Nanotechnology-enabled photochemical immune stimulation in clinical veterinary models of head and neck cancers

Abstract Background: Photodynamic therapy (PDT) is a non-surgical treatment using light to activate the cytotoxicity of a photosensitizing drug in cancer cells. PORPHYSOMES (PS) are lipid-porphyrin nanoparticles with high tumor uptake and PDT efficacy as well as low skin sensitivity. We have shown that activating PS with ‘sub-therapeutic’ PDT light dose in mouse models of head and neck (H&N) cancer stimulates immunogenic cell death and generates robust and transferable anti-tumor immunity. Here, we demonstrate the first evidence of this photochemical immune stimulation (PCIS) using PS in veterinary patients with spontaneous H&N tumors. Methods: Clinical veterinary trials were conducted at the Ontario Veterinary College (AUP# 4548) in companion dogs with resectable H&N cancers. PS were injected IV at 3 mg/kg. Subjects in Arm 1 of the trial underwent surgery 24-48 h post injection. Subjects in Arm 2 underwent sub-therapeutic PDT treatment (671 nm, 12.5∼50 J interstitial fiber or 12.5∼25 J/cm2 surface) at 6 or 24 h post injection, followed by resection at 48 h post injection. Blood samples were collected for hematology, biochemistry, pharmacokinetic analysis and immune profiling. During surgery, the tumor and neck lymph nodes were imaged by fluorescence for PS localization before submission for pathology. Cytokine and chemokine levels were measured in plasma/serum pre and post PDT, and tumor and lymph nodes were analyzed to compare for immune cell changes between Arms 1 (control) and 2. Results: Eight veterinary patients were recruited: 6 thyroid carcinomas, 1 oral squamous cell carcinoma, 1 oral melanoma. Three subjects were enrolled in Arm 1 and 5 in Arm 2. No significant changes in blood counts or biochemistry were detected in any dog post PS injection. The PS half-life in plasma was ∼57 h, and the tumor uptake varied between 6 and 60 µg/g (mean 28 µg/g). PDT was well tolerated in all cases, with no treatment-related adverse effects reported. Increases in multiple proinflammatory cytokines and chemokines were detected within 24 h of PDT, including significant increases in IL-8 and TNF alpha. Histology confirmed enrichment in CD68+ macrophages and CD16+ neutrophils in the PDT-treated tumors and in multiple T cell populations in lymph nodes. The relative magnitude of immune responses post PDT correlated weakly with PDT light dose in this small dataset. Of the subjects treated with PDT (7 mo. longest follow-up to date), only 1 tumor recurrence (in lung) was reported. Conclusions: PS injection and PDT treatments were well tolerated. Sub-therapeutic PDT simulated measurable immune responses in these spontaneous veterinary tumors, analogous to the early responses seen in mouse models, in which the impacts on tumor progression, metastasis and survival were significant. These data provide key proof of concept evidence for PS PCIS in H&N cancers and motivate the continue translation of PS into human clinical studies. Citation Format: Michael S. Valic, Charly J. McKenna, Mark Zheng, Jason L. Townson, Harley H. Chan, Layla Pires, Bridget Bane, Sharon Tzelnick, Alessandra Ruaro, Axel Sahovaler, Brian C. Wilson, Michelle L. Oblak, Jonathan C. Irish, Gang Zheng. Nanotechnology-enabled photochemical immune stimulation in clinical veterinary models of head and neck cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7266.