Antigen-specific T cell Redirectors: a nanoparticle based approach for redirecting T cells

Abstract

Redirection of T cells to target and destroy tumors has become an important clinical tool and major area of research in tumor immunology. Here we present a novel, nanoparticle-based approach to selectively bind antigen-specific cytotoxic T cells (CTL) and redirect them to kill tumors, termed ATR (Antigen-specific T cell Redirectors). ATR were generated by decorating nanoparticles with both an antigen-specific T cell binding moiety, either peptide loaded MHC-Ig dimer or clonotypic anti-TCR antibody, and a model tumor cell binding moiety, anti-CD19 antibody to engage CD19+ tumor cells. ATR stably bind tumor cells and CTL in a dose dependent fashion and stimulate antigen-specific conjugate formation between those cells. ATR induced redirected lysis of tumor cells in vitro, as demonstrated by 51Cr-release killing. In vivo ATR administration led to reduced tumor growth in a SCID/beige human lymphoma treatment model. In summary, ATR represent a novel, nanoparticle based approach for redirecting antigen-specific CTL to kill tumors.

DOI: 10.18632/oncotarget.11785

Cite this paper

@inproceedings{Schuetz2016AntigenspecificTC, title={Antigen-specific T cell Redirectors: a nanoparticle based approach for redirecting T cells}, author={Christian Schuetz and Juan Carlos Varela and Karlo Perica and Carl Haupt and Mathias Oelke and Jonathan P Schneck}, booktitle={Oncotarget}, year={2016} }