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Antigen-specific T cell redirectors (ATR) for antigen-specific redirection of T cells to tumors

Antigen-specific T cell redirectors (ATR) for antigen-specific redirection of T cells to tumors Schütz et al. Journal for ImmunoTherapy of Cancer 2014, 2(Suppl 3):P36 http://www.immunotherapyofcancer.org/content/2/S3/P36 POSTER PRESENTATION Open Access Antigen-specific T cell redirectors (ATR) for antigen-specific redirection of T cells to tumors 1* 2 3 1 1 1 Christian Schütz , Karlo Perica , Juan Varela , Carl Haupt , Mathias Oelke , Jonathan Schneck From Society for Immunotherapy of Cancer 29th Annual Meeting National Harbor, MD, USA. 6-9 November 2014 Immunotherapy is the modulation of a patient’s immune injection induced T cell re-direction and reduced tumor system to treat illness. Unfortunately many T cell based growth in a s.c. Raji/SCIDbeige treatment model. attempts have failed due to the fact that existing tumor- In summary this data demonstrates that ATR target and specific T cells are mostly anergic or tolerized and ex vivo redirect antigen-specific CTL to tumor cells that would generated T cells are often already of exhausted pheno- otherwise not be recognized and mediates their lysis. ATR type. Therefore, investigators have developed alternative can be used to develop new innovative immunotherapeu- approaches including bispecific antibody technology to tic approaches for all cancers that can be targeted with redirect fully functional non-tumor specific T cells to the antibodies or antibody-like molecules. Furthermore, ATR tumor. This has been primarily accomplished through tar- could also be used in conjunction with virus-specific geting CD3, which is expressed on all T cells to engage immunization to specifically increase the targeted CTL and redirect them towards a molecule that is expressed on population. Ultimately, we expect ATR and their potential thetumor cells.Herewepresent anovel nanoparticle for clinical applications to increase our understanding of based approach to selectively target cytotoxic T cells tumor immunotherapy through T cell redirection. (CTL) and re-direct them to kill tumors, termed ATR (Antigen-specific T cell Redirectors). Authors’ details ATR were generated by coupling either MHC-Ig dimer 1 Johns Hopkins School of Medicine, Department of Pathology, Institute for or clonotypic anti-TCR antibody 1B2 to target the effector Cell Engineering, United States. Johns Hopkins School of Medicine, Department of Biomedical Engineering, Institute for Cell Engineering, United T cell population and an anti-CD19 to re-direct those to States. Johns Hopkins School of Medicine, United States. CD19+ tumor target cells onto 50-100nm nanoparticles. Flow cytometry and microscope based data confirm that Published: 6 November 2014 the described ATR phenotype efficiently and stably stain tumor and T cells in a dose dependent manner, and ATR mediate antigen-specific conjugate formation of effector doi:10.1186/2051-1426-2-S3-P36 Cite this article as: Schütz et al.: Antigen-specific T cell redirectors (ATR) T cells and tumor target cells. We further developed two for antigen-specific redirection of T cells to tumors. Journal for clinically relevant protocols to test and optimize our ATR ImmunoTherapy of Cancer 2014 2(Suppl 3):P36. in vitro. First a pre-treatment approach in which the effec- tor T cells are pre-incubated with ATR mimicking an adoptive transfer approach and second a co-culture proto- col that mimics an active immunotherapy approach of direct ATR injection. Antigen-specific ATR mediated re- direction of T cells to tumor target cells was demonstrated in Cr-release killing assays at low E:T ratios. Variation of ATR target-cell: effector-cell targeting molecule ratio could further increase efficacy. Finally, intra tumoral ATR Johns Hopkins School of Medicine, Department of Pathology, Institute for Cell Engineering, United States Full list of author information is available at the end of the article © 2014 Schütz et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal for ImmunoTherapy of Cancer Springer Journals

Antigen-specific T cell redirectors (ATR) for antigen-specific redirection of T cells to tumors

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Publisher
Springer Journals
Copyright
Copyright © 2014 by Schütz et al.; licensee BioMed Central Ltd.
Subject
Medicine & Public Health; Oncology
eISSN
2051-1426
DOI
10.1186/2051-1426-2-S3-P36
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Abstract

Schütz et al. Journal for ImmunoTherapy of Cancer 2014, 2(Suppl 3):P36 http://www.immunotherapyofcancer.org/content/2/S3/P36 POSTER PRESENTATION Open Access Antigen-specific T cell redirectors (ATR) for antigen-specific redirection of T cells to tumors 1* 2 3 1 1 1 Christian Schütz , Karlo Perica , Juan Varela , Carl Haupt , Mathias Oelke , Jonathan Schneck From Society for Immunotherapy of Cancer 29th Annual Meeting National Harbor, MD, USA. 6-9 November 2014 Immunotherapy is the modulation of a patient’s immune injection induced T cell re-direction and reduced tumor system to treat illness. Unfortunately many T cell based growth in a s.c. Raji/SCIDbeige treatment model. attempts have failed due to the fact that existing tumor- In summary this data demonstrates that ATR target and specific T cells are mostly anergic or tolerized and ex vivo redirect antigen-specific CTL to tumor cells that would generated T cells are often already of exhausted pheno- otherwise not be recognized and mediates their lysis. ATR type. Therefore, investigators have developed alternative can be used to develop new innovative immunotherapeu- approaches including bispecific antibody technology to tic approaches for all cancers that can be targeted with redirect fully functional non-tumor specific T cells to the antibodies or antibody-like molecules. Furthermore, ATR tumor. This has been primarily accomplished through tar- could also be used in conjunction with virus-specific geting CD3, which is expressed on all T cells to engage immunization to specifically increase the targeted CTL and redirect them towards a molecule that is expressed on population. Ultimately, we expect ATR and their potential thetumor cells.Herewepresent anovel nanoparticle for clinical applications to increase our understanding of based approach to selectively target cytotoxic T cells tumor immunotherapy through T cell redirection. (CTL) and re-direct them to kill tumors, termed ATR (Antigen-specific T cell Redirectors). Authors’ details ATR were generated by coupling either MHC-Ig dimer 1 Johns Hopkins School of Medicine, Department of Pathology, Institute for or clonotypic anti-TCR antibody 1B2 to target the effector Cell Engineering, United States. Johns Hopkins School of Medicine, Department of Biomedical Engineering, Institute for Cell Engineering, United T cell population and an anti-CD19 to re-direct those to States. Johns Hopkins School of Medicine, United States. CD19+ tumor target cells onto 50-100nm nanoparticles. Flow cytometry and microscope based data confirm that Published: 6 November 2014 the described ATR phenotype efficiently and stably stain tumor and T cells in a dose dependent manner, and ATR mediate antigen-specific conjugate formation of effector doi:10.1186/2051-1426-2-S3-P36 Cite this article as: Schütz et al.: Antigen-specific T cell redirectors (ATR) T cells and tumor target cells. We further developed two for antigen-specific redirection of T cells to tumors. Journal for clinically relevant protocols to test and optimize our ATR ImmunoTherapy of Cancer 2014 2(Suppl 3):P36. in vitro. First a pre-treatment approach in which the effec- tor T cells are pre-incubated with ATR mimicking an adoptive transfer approach and second a co-culture proto- col that mimics an active immunotherapy approach of direct ATR injection. Antigen-specific ATR mediated re- direction of T cells to tumor target cells was demonstrated in Cr-release killing assays at low E:T ratios. Variation of ATR target-cell: effector-cell targeting molecule ratio could further increase efficacy. Finally, intra tumoral ATR Johns Hopkins School of Medicine, Department of Pathology, Institute for Cell Engineering, United States Full list of author information is available at the end of the article © 2014 Schütz et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Journal

Journal for ImmunoTherapy of Cancer – Springer Journals

Published: Nov 6, 2014

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