Abstract 4531: Nanoscale Artificial Antigen Presenting Cells for T Cell Immunotherapy.

Abstract

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

Synthetic Antigen-Presenting Cells for Adoptive T Cell Therapy

“…However, for TIL therapy, nonspecific stimulation by αCD3/αCD28 results in the activation of both tumor-specific and non-specific clones, leading to an overall decrease in antigen-specificity and limiting the ability of tumor-specific T cells to persist post-transfusion. [11][12][13] More sophisticated strategies for selective activation and expansion of antigen-specific T cells involve the use of magnetic nanoparticles [13][14][15][16] or 3D-scaffolds [17][18] decorated with major histocompatibility complexes (MHCs) presenting disease-specific peptides.…”

“…These pMHC-based materials have been shown to be able to rapidly activate and expand lowfrequency antigen-specific T cell populations directly from mouse splenocytes or human PBMCs, producing cells capable of potent cytotoxic activity in pre-clinical models. [13][14][17][18] Recombinant pMHC molecules are typically used as multimeric complexes to analyze or sort antigen-specific T cells by flow-, mass-, or DNA-based cytometry. [19][20][21][22][23] Here we develop synthetic antigen-presenting cells (synAPCs) comprising liposomes surface-conjugated with pMHC molecules for antigen-specific activation of T cells.…”