Abstract 2529: Targeted light-activable multi-agent nanoparticle for enhanced photoimmunotherapy treatment of peritoneal metastasis

Abstract Background: Peritoneal metastasis is the result of direct shedding of tumor cells from ovarian, colorectal, and other cancers that lead to studding and growth on the peritoneal surfaces and abdominal organs. Standard chemotherapy and surgery can transiently improve symptoms, but long-term disease control and survival extension remain rare due to residual disease and treatment resistance. In the past 40 years, tremendous progress in photoimmunotherapy (PIT) has been made to treat metastasis. However, many are lost in translation due to heterogeneity in photosensitizer drug uptake and treatment response. Thus, we hypothesize that the delivery of targeted therapies with a multimodal approach for PIT and integrates well with current standards of care strategies can help overcome heterogeneous delivery and improved treatment efficacy. Our novel targeted photoactivable multi-agent liposome (TPMAL) combined with fluorescence-guided PIT was demonstrated in this newly reported study. Methods: TPMAL consists of antibody drug conjugates (photosensitizer drug and anti-EGFR antibody) conjugated onto active-loaded liposomal surface. Female athymic nude mice (18-20 g and 4-6 weeks old) were injected intraperitoneally with 3 x 107 OVCAR-5 human ovarian cancer cells suspended in 2 mL of PBS. Post tumor implantation, mice were i.p. injected with TPMAL or ADC alone on Day 10. Post 24h, tumor nodules were collected and frozen with Tissue-Tek O.C.T compound at -80°C until slicing. Fluorescence and bright field imaging of whole tumor nodule slices were performed with a Lionheart™ FX Automated Microscope. The center of each tumor nodule was selected for further image analysis using ImageJ. Lastly, intraperitoneal fluorescence-guided light delivery PIT with TPMAL was performed using the ML7710 medial laser device and Modulight cloud software for survival studies. Results: TPMAL active-loaded formulation demonstrated batch-to-batch consistency and stability was observed for up to one year. This formulation also demonstrated enhanced photosensitizer drug delivery into peritoneal tumor nodules by 1.6X and up to 616.4 μm penetration depth compared to antibody drug conjugates alone. TPMAL FGLD PIT combination therapy with adjuvant chemotherapy also demonstrated enhanced long-term survival by 240X compared to no treatment and chemotherapy alone groups. Conclusions: Our novel targeted photoactivable multi-agent liposome (TPMAL) combined with fluorescence-guided PIT was investigated for its translational potential and therapeutic efficacy by (1) developing an active-loaded liposomal formulation, (2) studying tumor nodule penetration depth of TPMAL, (3) understanding tissue optical property via oxygenation and how it may affect PIT using the ML7710, and (4) enhancing long term therapeutic efficacy compared to monotherapy treated groups in a mouse peritoneal carcinomatosis model. Citation Format: Sumiao Pang, Carla Arnau Del Valle, Robert Perttila, Nada Fadul, Dana Roque, Tayyaba Hasan, Petteri Uusimaa, Huang Chiao` Huang. Targeted light-activable multi-agent nanoparticle for enhanced photoimmunotherapy treatment of peritoneal metastasis [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 2529.