Using nanoparticles as artificial antigen-presenting cells to activate human CD4 T cells for immunotherapy 4447

Abstract Description CD4 T cell-based adoptive cell transfer (ACT) therapies have shown clinical success across multiple cancer types. However, finding methods to expand the rare antigen-specific precursor population remains challenging. Here, we developed nanoscale artificial antigen-presenting cells (aAPCs) to expand human antigen-specific CD4 T cells in vitro. These aAPCs are nanoscale beads conjugated with MHC class II and the co-stimulatory molecule, anti-CD28. We used aAPCs to stimulate human CD4 T cells and have demonstrated that this system significantly increases the frequency of antigen-specific CD4 T cells. Specifically, we successfully expanded tetanus toxoid (p30)-specific and herpes simplex virus (HSV)-specific CD4 T cells from healthy human PBMCs with aAPC. After 21 days of expansion, the antigen-specific population showed substantial proliferation, enriching from 1% to 10% for HSV and exceeding 30% for p30. The resulting antigen-specific CD4 T cells secrete high levels of effector cytokine, including TNF-α, IFN-γ, IL-2, and granzyme B. These CD4 T cells demonstrated antigen-specific cytotoxicity when co-cultured with cognate target cells with a 60% antigen-specific killing capability. Furthermore, these CD4 T cells are predominantly effector memory T cells, which provide sustained immune response in ACT. Our study shows that the aAPC platform effectively expands low-frequency, antigen-specific CD4 T cells, advancing antigen-specific ACT strategies for cancer. Funding Sources Supported by Government Scholarship for Doctoral Programs Overseas, Ministry of Education, Taiwan, and Predoctoral Fellowship in Drug Delivery from PhRMA Foundation. Topic Categories Technological Innovations in Immunology (TECH)