TNF-α based adoptive T cell therapy
Slava Stamova1*, Christoph Reissfelder2, Torsten Reichert3, Gerrit Spanier3, Petra Hoffmann4 and Philipp Beckhove1
1Regensburg Center for Interventional Immunology, University Regensburg, Germany; 2Department of General, Visceral and Transplantation Surgery University Heidelberg, Germany; 3Department for Maxillofacial Surgery University Hospital Regensburg, Germany; 4Internal Medicine III/ Hematology and Internal Oncology, University Hospital Regensburg, Germany
The extent of T cell infiltrates in the primary tumor is an important prognostic factors in many cancer entities. Still, how exactly the T cell infiltrates influence the patient survival remains unclear. To answer this question we investigated the presence and functional activity of tumor infiltrating lymphocytes (TILs) as well as their specificity in colorectal cancer (CRC) patients and correlated the obtained results to long term survival. We have demonstrated that tumor necrosis factor alpha (TNF-α) expression characterizes a population of tumor specific, in situ active cytotoxic T cells. We have also observed that the presence of these TNF-α expressing TILs correlates with increased TNF-α concentration in CRC tumors, making intratumoral TNF-α concentration a direct indicator of the in situ functionality of T cells in CRC. Furthermore in a retrospective multivariate analysis in CRC patients we have determined that the intratumoral TNF-α concentration is an independent prognostic factor in CRC.
Based on these observations, we have hypothesized that TNF-α-secreting T cells possess therapeutic potential and we could utilize them for adoptive T cell therapy.
We are currently investigating the presence of TNF-α-secreting T cells in other tumor entities such as head and neck squamous cell carcinoma (HNSCC) and we are optimizing protocols for their isolation and expansion. We are aiming to utilize a prognostically relevant and functionally effective subset of T cells, which are highly reactive and recognize a broad spectrum of tumor antigens, thus making them a powerful tool toward efficient T cell based immunotherapy.