Antigen-specific T Cell Redirectors: a Nanoparticle Based Approach for Redirecting T Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Sep 8

PMID 27602488

Citations 15

Authors

Christian Schutz

Juan Carlos Varela

Karlo Perica

Carl Haupt

Mathias Oelke

Jonathan P Schneck

Affiliations

Soon will be listed here.

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.

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