Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice
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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.
KeywordsAdoptive immunotherapy chimeric antigen receptor SPECT-CT
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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