Antigen-specific T cell Redirectors: a nanoparticle based approach for redirecting T cells
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Christian Schütz1,4, Juan Carlos Varela2, Karlo Perica1, Carl Haupt1, Mathias Oelke1,3, Jonathan P. Schneck1
1Institute of Cell Engineering and Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
2Division of Hematology, Department of Medicine, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland, USA
3NexImmune Inc., Gaithersburg, Maryland, USA
4Current address: Division of Immunology, Paul-Ehrlich-Institut, Langen, Germany
Jonathan P. Schneck, email: [email protected]
Christian Schütz, email: [email protected]
Keywords: cancer, redirection, antigen-specific T cells, nanoparticle, MHC-Ig
Received: March 07, 2016 Accepted: July 27, 2016 Published: September 01, 2016
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.
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