Pamplona, January 20th. Researchers at the Center for Applied Medical Research (CIMA) at the University of Navarra and the Spanish National Center for Cardiovascular Research (CNIC) have discovered mechanisms which contribute to the anti-tumor response of the immune system.  The results of this work were published in the latest issue of the scientific journal Cancer Discover (January 8th), ranked 5th of 211 journals with regards to Impact Factor in the Oncology category in 2015 according to Thomson Reuters' Journal Citation Report.

The anti-gen presenting cells are responsible for initiating and regulating the immune system against pathogens and tumors. However, the tumors develop mechanisms to elude the control of the immune system, silencing the response of the cytotoxic T lymphocytes which destroy the tumors.

Over the last few years it has been found that the use of "immune-activating" antibodies that reactivate the silenced cytotoxic T lymphocytes can stimulate a potent anti-tumor response.  "In this work we have discovered that the production of cytotoxic T cells which can be ‘rescued' by immunotherapy with anti-PD1 and anti-CD137 antibodies depends on a specific sub-group of anti-gen presenting cells. These are dendritic cells depending on the Batf3 transcription factor, which take antigens from the tumor cells and present them to the T lymphocytes, and so attain the capacity to eliminate the tumor", explained Dr. Ignacio Melero, a researcher at CIMA and the Clínica University of Navarra, co-director of the research work, which is part of the doctoral thesis of Alfonso Rodríguez.

Recently the efficacy of anti-PD-1 antibodies has been shown in the treatment of metastatic melanoma and non-small cell lung cancer first line treatment. According to David Sancho, a researcher at the CNIC and co-director of the study, "finding the presenting cell that promotes the anti-tumor immune response will permit us to design strategies to increase the efficacy of treatment with immune-activating antibodies and to find bio-markers that will predict which patients can benefit from the treatment. Our work suggests that these Batf3-dependent dendritic cells may be fundamental in anti-tumor immunotherapy".

The result is the fruit of the experience of the CNIC and the University of Navarra regarding the mechanisms of antigen presentation and cancer immunotherapy, respectively.

Clinical application

The CIMA and the Clínica University of Navarra researchers are coordinating a European project, in which the CNIC also participates, with the aim of obtaining these antigen presenting cells in the blood of patients with tumors through the use of cell selection techniques and the formulation of specific vaccines for the patient's tumor.  "We have seen that the number of these cells increase when using a growth factor called FLT-3L, and by means of this agent we could increase their number in patients receiving anti-PD-1 or anti-CD137 antibodies to strengthen effectiveness through combined therapy", claims Dr. Melero.
If the results are confirmed, the researchers are contemplating the use of these cells in cell therapy. "We would also like to study whether this mechanism is negative in patients who do not respond to treatment with anti-PD-1. Our hypothesis is that the response to anti-PD-1 correlates with the presence of this sub-group of dendritic cells in the tumor tissue", the researchers explain.

The same issue of Cancer Discovery includes a commentary "In the Spotlight", by Dr. Daniel Speiser, on the findings of the Spanish groups, in which he emphasizes the importance of these findings in achieving greater efficacy in cancer immunotherapies that have already been approved for clinical use and are being developed for multiple uses in oncology.   

Caption: (From right to left) Dr. Ignacio Melero and Alfonso Sánchez

 

For further information or to request interview, please contact:

Miriam Salcedo: Chief Communication Officer, miriamsalcedo@unav.es

María Pilar Huarte: CIMA Communications, mphuarte@unav.es

(+34) 948 194 700 Ext. 5026

 

Attached there two audios of Dr. Melero testimony:

·         Audio #1  Areas that have been revolutionized by immunotherapy, 36".

·         Audio #2  Purposes of the research, 36".