Research Assistant University of Georgia Athens, Georgia
Triple-negative breast cancer (TNBC) is one of the most aggressive and treatment-resistant subtypes of breast cancer affecting women in the United States. T-cell exhaustion has been identified as a key factor contributing to therapeutic failure, particularly in immunotherapy. This presentation highlights the nonclinical investigation of novel PD-1–linked calcium nanoparticles as a strategy to target T-cell exhaustion in TNBC.
Flow cytometry, confocal microscopy, single-cell sequencing, and immunoblotting analyses confirm that the nanoparticles effectively bind to human CD8⁺ T cells and enhance their cytotoxic function through the NF-κB and NFAT signaling pathways. This enhanced activity significantly decreased the viability of 3D patient-derived tumor organoids and humanized (PDx) mouse models, without any additional systemic toxicities observed.
Learning Objectives:
Upon completion, participant will be able to understand the current treatment landscape of triple-negative breast cancer (TNBC).
Upon completion, participant will be able to identify key factors contributing to immunotherapy resistance in TNBC.
Upon completion, participant will be able to describe the scientific rationale and strategy behind the development of novel PD-1–linked calcium nanoparticles.
Upon completion, participant will be able to discuss the importance of adopting human-relevant new approach methodologies (NAMs) in nonclinical research
Upon completion, participants will be able to evaluate the impact of emerging technologies and recent regulatory considerations governing the adoption of human-relevant new approach methodologies (NAMs) in nonclinical and clinical research.
