Immunosuppressant Cell Inhibitors and Design of Immunostimulant Chimeras
One of the main characteristics of chronic infections and cancer is the expression of immunosuppressant molecules, which inhibit the development of an efficient immune response that can eliminate the infectious agent or the tumor. CD4+CD25+FOXP3+ regulatory T (nTreg) cells play an essential role in the control of the immune system and in the control of autoimmune diseases. However, their activity suppresses the activation of antitumor immune responses. Our group has identified FOXP3 transcription factor inhibiting peptides (patents ES 200703052 and ES 201230309) that block the action of the T regulatory cells and even potentiate the function of the CD4 effector T cells. Their utility is currently being analyzed in vivo in different immunotherapy models. We have also begun a program to identify small molecules that block the activity of the Treg cells, in order to develop antitumor therapies.
Furthermore, immunotherapy based on adoptive transfer of T cells unequivocally shows that, in some types of tumors, such as melanoma, T cells may achieve a lasting antitumor response, even in situations of advanced metastasis. However, these strategies are not effective in other types of tumors. The immunosuppressant mechanisms induced by these tumors may be responsible for this lack of efficacy. Our group is working on alternative ways of increasing the efficacy of adoptive transfer by genetically modifying the T cells using immunostimulant chimeric receptors. These genetically modified cells may overcome the immunosuppression induced by the tumor and eradicate the malignant tumor cells.