title: Cytotoxic T lymphocyte trafficking and survival in an augmented fibrin matrix carrier.
abstract: Cell-based therapies have intriguing potential for the treatment of a variety of neurological disorders. One such example is genetically engineered cytotoxic T lymphocytes (CTLs) that are being investigated in brain tumor clinical trials. The development of methods for CTL delivery is critical to their use in the laboratory and clinical setting. In our study, we determined whether CTLs can migrate through fibrin matrices and if their migration, survival, and function could be modulated by adding chemokines to the matrix. Our results indicated that CTLs can freely migrate through fibrin matrices. As expected, the addition of the monocyte chemotactic protein-1 (MCP-1), also known as chemokine C-C motif ligand 2 (CCL2), to the surrounding media increased egress of the CTLs out of the fibrin clot. Interleukin (IL) -2 and/or IL-15 embedded in the matrix enhanced T cell survival and further promoted T cell migration. The interleukin-13 receptor alpha 2 specific (IL-13R alpha2) T cells that traveled out of the fibrin clot retained the capacity to kill U251 glioma cells. In summary, CTLs can survive and migrate robustly in fibrin matrices. These processes can be influenced by modification of matrix constituents. We conclude that fibrin matrices may be suitable T cell carriers and can be used to facilitate understanding of T cell interaction with the surrounding microenvironment.
authors.affiliation: Division of Neurosurgery, City of Hope National Medical Center, Duarte, California, United States of America.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Zou
authors.forename: Erin
authors.initials: E
authors.lastname: Denny
authors.forename: Christine E
authors.initials: CE
authors.lastname: Brown
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jensen
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Fujii
authors.forename: Josh
authors.initials: J
authors.lastname: Neman
authors.forename: Rahul
authors.initials: R
authors.lastname: Jandial
authors.forename: Mike
authors.initials: M
authors.lastname: Chen
mesh_terms: D001932:Brain Neoplasms / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology; D005337:Fibrin / Q000276:immunology*; D005910:Glioma / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C569274:IL15 protein, human; C508594:IL2 protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D005337:Fibrin