Artificial antigen presenting cells (aAPC), which deliver stimulatory signals to cytotoxic lymphocytes, are a powerful tool for both adoptive and active immunotherapy. Thus far, aAPC have been synthesized by coupling T cell activating proteins such as CD3 or MHC-peptide to micron-sized beads. Nanoscale platforms have different trafficking and biophysical interaction properties and may allow development of new immunotherapeutic strategies. We therefore manufactured aAPC based on two types of nanoscale particle platforms: biocompatible iron-dextran paramagnetic particles (50–100 nm in diameter) and avidin-coated quantum dot nanocrystals, (~30 nm). Nanoscale aAPC induced antigen-specific T cell proliferation from mouse splenocytes and human peripheral blood T cells. When injected in vivo, both iron-dextran particles and quantum dot nanocrystals enhanced tumor rejection in a subcutaneous mouse melanoma model. This is the first description of nanoscale aAPC that induce antigen-specific T cell proliferation in vitro and lead to effective T cell stimulation and inhibition of tumor growth in vivo.

Artificial antigen presenting cells (aAPC), which deliver stimulatory signals to cytotoxic lymphocytes, are a powerful tool for adoptive immunotherapy and in vivo T cell stimulation. Thus far, bead-based aAPC have been synthesized by coupling T cell activating proteins such as CD3 or MHC-peptide to beads several microns in diameter. By reducing the size of aAPC, we anticipated more efficient delivery of these stimulatory signals to tumor and lymph nodes where antigen-specific T cells reside. We thus manufactured aAPC based on two nanoscale particle platforms: biocompatible iron-dextran paramagnetic particles, 50-100 nm in diameter, and avidin-coated quantum dot nanocrystals, less than 20 nm in diameter. Nanoscale aAPC induced antigen-specific T cell proliferation from both TCR transgenic mouse splenocytes and human, polyclonal peripheral blood T cells. In a subcutaneous mouse melanoma model, both iron-dextran particles and quantum dot nanocrystals mediated tumor rejection when injected in vivo. To our knowledge, this is the first description of a nanoscale, particle-based aAPC that induces T cell proliferation in vitro and leads to effective T cell stimulation and tumor rejection in vivo. Furthermore, nano-aAPC represent a novel platform for studying receptor-ligand interactions at the membrane-nanoparticle interface. Citation Format: Karlo Perica, Joan G. Bieler, Andrés De León Medero, Yen-Ling Chiu, Malarvizhi Durai, Michaela Niemöller, Mario Assenmacher, Anne Richter, Mathias Oelke, Jonathan Schneck. Nanoscale Artificial Antigen Presenting Cells for T Cell Immunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4531. doi:10.1158/1538-7445.AM2013-4531