title: Trafficking of CAR-engineered human T cells following regional or systemic adoptive transfer in SCID beige mice.
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.
authors.affiliation: The CAR Mechanics Group, King's College London School of Medicine, Guy's Hospital Campus, St Thomas Street, London, SE1 9RT, UK.
authors.forename: Ana Caterina
authors.initials: AC
authors.lastname: Parente-Pereira
authors.forename: Jerome
authors.initials: J
authors.lastname: Burnet
authors.forename: David
authors.initials: D
authors.lastname: Ellison
authors.forename: Julie
authors.initials: J
authors.lastname: Foster
authors.forename: David Marc
authors.initials: DM
authors.lastname: Davies
authors.forename: Sjoukje
authors.initials: S
authors.lastname: van der Stegen
authors.forename: Sophie
authors.initials: S
authors.lastname: Burbridge
authors.forename: Laura
authors.initials: L
authors.lastname: Chiapero-Stanke
authors.forename: Scott
authors.initials: S
authors.lastname: Wilkie
authors.forename: Stephen
authors.initials: S
authors.lastname: Mather
authors.forename: John
authors.initials: J
authors.lastname: Maher
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects* / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D018396:Mucin-1 / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins