Trafficking of CAR-Engineered Human T Cells Following Regional or Systemic Adoptive Transfer in SCID Beige Mice
Ana Caterina Parente-Pereira, Jerome Burnet, David Ellison, Julie Foster, David Marc Davies, Sjoukje van der Stegen, Sophie Burbridge, Laura Chiapero-Stanke, Scott Wilkie, Stephen Mather, John Maher
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.