cytotoxic t lymphocyte trafficking and survival in an augmented fibrin matrix carrier细胞毒性t淋巴细胞贩运和生存在一个增广矩阵纤维蛋白载体.pdfVIP

Cytotoxic T Lymphocyte Trafficking and Survival in an Augmented Fibrin Matrix Carrier 1 1 2 2 1 1 Zhaoxia Zou , Erin Denny , Christine E. Brown , Michael C. Jensen , Gang Li , Tatsuhiro Fujii , 1 1 1 Josh Neman , Rahul Jandial , Mike Chen * 1 Division of Neurosurgery, City of Hope National Medical Center, Duarte, California, United States of America, 2 Department of Cancer Immunotherapeutics Tumor Immunology, City of Hope National Medical Center, Duarte, California, United States of America 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 migrat