Abstract 6897: Development of immunomodulatory nanoparticles targeting HER2 for breast cancer therapy

Abstract Nanoparticles (NPs) are emerging as a promising strategy in oncology, offering optimised drug delivery and the potential to modulate immune responses. In this study, we developed an innovative nanoparticle encapsulating docetaxel and functionalised with trastuzumab for the precise targeting of HER2-positive tumours (called ANC for Antibody Nanoparticle Conjufate). Pharmacokinetic analyses were performed using C57BL/6 mice, which were administered free docetaxel (1.6 mg/kg) and trastuzumab (135 ng/kg) via intraperitoneal injection (n = 29), or ANC (nanoparticles at the same docetaxel and trastuzumab doses as the free drugs, n = 40). Blood samples were collected at 0.5, 1, 2, 3, 6, 8, 12, and 24 hours post-injection, and the frozen plasma was analysed using by HPLC-UV. For biodistribution studies, DiR-labelled nanoparticles were administered to C57BL/6 mice, and imaging was performed on a daily basis using an IVIS Spectrum imager. Immunomodulation study was assessed by flow cytometry. The AUC0-∞ for the ANC (4250.79 ng.mL/h) was four times higher than for free docetaxel (1050.3 ng.mL-1.h-1). In addition, the half-life of the liposomal docetaxel (22.14 hours) was significantly three times longer than that of the free docetaxel (7.15 hours). Biodistribution studies in mouse models showed that the nanoparticle remained stable and did not reach the liver until 30 hours after injection. Immunomodulation studies showed that ANC had a different effect on the distribution of lymphocyte subpopulations compared to free drug, with a notable decrease in regulatory T cells (Tregs) in the ANC-treated group, suggesting a potential immunostimulatory effect. The potential immunomodulatory effects of these nanoparticles on anti-tumour immune responses are currently being investigated. These preliminary results demonstrate the dual benefit of targeted drug delivery and immune system engagement offored by these nanoparticles, which could pave the way for novel breast cancer treatments. Citation Format: Mathilde Dacos, Lea Plantureux, Erwan Diroff, Sarah Giacometti, Joseph Ciccolini, Raphaelle Fanciullino. Development of immunomodulatory nanoparticles targeting HER2 for breast cancer therapy [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 6897.