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Dendritic cells pulsed with RNA encoding allogeneic MHC and antigen induce T cells with superior antitumor activity and higher TCR functional avidity

Official URL:https://doi.org/10.1182/blood-2009-03-209387
PubMed:View item in PubMed
Creators Name:Wilde, S. and Sommermeyer, D. and Frankenberger, B. and Schiemann, M. and Milosevic, S. and Spranger, S. and Pohla, H. and Uckert, W. and Busch, D.H. and Schendel, D.J.
Journal Title:Blood
Journal Abbreviation:Blood
Page Range:2131-2139
Date:3 September 2009
Keywords:Adoptive Transfer, Neoplasm Antigens, Tumor Cell Line, Dendritic Cells, HLA Antigens, Isoantigens, Neoplasms, Peptides, RNAT-Cell Antigen Receptors, T-Lymphocytes, Transfection
Abstract:Adoptive transfer of T cells expressing transgenic T cell receptors (TCR) with anti-tumor function is a hopeful new therapy for patients with advanced tumors however there is a critical bottleneck in identifying high-affinity TCR specificities needed to treat different malignancies. We have developed a strategy using autologous dendritic cells co-transfected with RNA encoding an allogeneic MHC molecule and a tumor-associated antigen (TAA) to obtain allo-restricted peptide-specific T cells having superior capacity to recognize tumor cells and higher functional avidity. This approach provides maximum flexibility since any MHC molecule and any TAA can be combined in the dendritic cells used for priming of autologous T cells. TCR of allo-restricted T cells when expressed as transgenes in activated peripheral blood lymphocytes transferred superior function compared with self-restricted TCR. This approach allows high-avidity T cells and TCR specific for tumor-associated self-peptides to be easily obtained for direct adoptive T cell therapy or for isolation of therapeutic transgenic TCR sequences.
Publisher:American Society of Hematology (U.S.A.)
Item Type:Article

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