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

C Schütz, JC Varela, K Perica, C Haupt, M Oelke… - Oncotarget, 2016 - ncbi.nlm.nih.gov
C Schütz, JC Varela, K Perica, C Haupt, M Oelke, JP Schneck
Oncotarget, 2016ncbi.nlm.nih.gov
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 …
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 51 Cr-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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