Antigen-specific T cell Redirectors: a nanoparticle based approach for redirecting T cells.
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.
Institute of Cell Engineering and Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.|Current address: Division of Immunology, Paul-Ehrlich-Institut, Langen, Germany.
Christian
C
Schütz
Division of Hematology, Department of Medicine, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
Juan Carlos
JC
Varela
Institute of Cell Engineering and Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Karlo
K
Perica
Institute of Cell Engineering and Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Carl
C
Haupt
Institute of Cell Engineering and Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.|NexImmune Inc., Gaithersburg, Maryland, USA.
Mathias
M
Oelke
Institute of Cell Engineering and Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Jonathan P
JP
Schneck
D000818:Animals; D000941:Antigens / Q000276:immunology*; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D006801:Humans; D008223:Lymphoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D053758:Nanoparticles / Q000737:chemistry*; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000941:Antigens; D018941:Antigens, CD19
MHC-Ig; antigen-specific T cells; cancer; nanoparticle; redirection