Adoptive
cell therapy (ACT) using in vitro expanded
tumor infiltrating T lymphocytes (TILs) from biopsy material represents a highly promising treatment of disseminated
cancer. A crucial prerequisite for successful ACT is sufficient recruitment of transferred lymphocytes to the
tumor site; however, despite infusion of billions of lymphocytes, T cell infiltration into the
tumor post ACT is limited. By PCR and Luminex analyses we found that a majority of
malignant melanoma (MM) cell lines expressed
chemokines CXCL1/Groα, CXCL8/IL-8, CXCL12/SDF-1 and CCL2. Concerning expression of the corresponding receptors on T cells, only the
IL-8 receptor, CXCR2, was not expressed on T cells. CXCR2 was therefore expressed in T cells by lentiviral transduction, and shown to lead to
ligand specific transwell migration of engineered T cells, as well as increased migration towards MM
conditioned medium. In vivo homing was assessed in a xenograft NOG mouse model. Mice with subcutaneous human
melanoma were treated with MAGE-A3 specific T cells transduced with either CXCR2 or MOCK. Transducing T cells carrying the MAGE-A3a3a high affinity
T cell receptor with CXCR2 increased
tumor infiltration. Flow cytometry analysis 7 days after ACT showed a doubling in CD3+ T cells in
tumor digest of mice receiving CXCR2 transduced T cells compared to MOCK treated mice, a finding confirmed by immunohistochemistry. In conclusion, our CXCR2 transduced T cells are functional in vitro and transduction with CXCR2 increases in vivo homing of T cells to
tumor site.