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Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice

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Abstract

Adoptive immunotherapy using chimeric antigen receptor-engrafted T cells is a promising emerging therapy for cancer. Prior to clinical testing, it is mandatory to evaluate human therapeutic cell products in meaningful in vivo pre-clinical models. Here, we describe the use of fused single-photon emission CT–CT imaging to monitor real-time migration of chimeric antigen receptor-engineered T cells in immune compromised (SCID Beige) mice. Following intravenous administration, human T cells migrate in a highly similar manner to that reported in man, but penetrate poorly into established tumors. By contrast, when delivered via intraperitoneal or subcutaneous routes, T cells remain at the site of inoculation with minimal systemic absorption—irrespective of the presence or absence of tumor. Together, these data support the validity of pre-clinical testing of human T-cell immunotherapy in SCID Beige mice. In light of their established efficacy, regional administration of engineered human T cells represents an attractive therapeutic option to minimize toxicity in the treatment of selected malignancies.

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Acknowledgements

We are very grateful to Dr Joy Burchell and Prof Joyce Taylor-Papadimitriou for provision of several highly useful MUC1-related reagents. This work was supported by the US Department of Defense (Fiscal Year 2008 Ovarian Cancer Research Program, Translational Research Partnership Award) under contract W81XWH-09-1-0096; Breast Cancer Campaign (project grant 2006NovPR18), Association for International Cancer Research (project grant 08-0419), Guy’s and St Thomas’ Charity, Experimental Cancer Medicine Centre (King’s College London) and from Guy’s and the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust.

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Authors and Affiliations

  1. The CAR Mechanics Group, King’s College London School of Medicine, Guy’s Hospital Campus, St Thomas Street, London, SE1 9RT, UK

    Ana Caterina Parente-Pereira, David Marc Davies, Sjoukje van der Stegen, Sophie Burbridge, Laura Chiapero-Stanke, Scott Wilkie & John Maher

  2. Centre for Molecular Oncology and Imaging, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BE, UK

    Jerome Burnet, David Ellison, Julie Foster & Stephen Mather

  3. Department of Immunology, Barnet and Chase Farm NHS Trust, Barnet, Hertfordshire, EN5 3DJ, UK

    John Maher

  4. Department of Clinical Immunology and Allergy, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, UK

    John Maher

  5. Research Oncology, Division of Cancer Studies, King’s College London School of Medicine, Guy’s Hospital Campus, Third Floor Bermondsey Wing, St Thomas Street, London, SE1 9RT, UK

    John Maher

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  1. Ana Caterina Parente-Pereira
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Correspondence to John Maher.

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Parente-Pereira, A.C., Burnet, J., Ellison, D. et al. Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice. J Clin Immunol 31, 710–718 (2011). https://doi.org/10.1007/s10875-011-9532-8

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  • DOI: https://doi.org/10.1007/s10875-011-9532-8

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