Aim5. Tailored immunotherapies
Based on the information that we will obtain in the previous phases, we will analyze the antitumor activity of novel combined immunotherapies. As explained, patients who relapse early or suffer a transformation have a poor outcome. For this reason, our goal is to determine which treatment combinations have better results in the different clinical groups.
Immunotherapies have entailed a change in oncology in the last few years, and comprise different types of treatments. One therapeutic approach that has been successful in certain types of cancer is the use of antibodies against immune checkpoint inhibitor (ICI). Immune checkpoints functions as breaks of T cells, responsible to attack tumor cells, and are frequently up-regulated in cancer. Thanks to therapeutic antibodies, these breaks are released and immune response may be reactivated.
Nevertheless, in any type of cancer, only a subset of patients responds to these therapies, partly depending on the TME. Moreover, in FL, data suggest that ICIs are not active as single agents, but good results have been reported in combination with rituximab. Thus, we will investigate which drug combinations may be beneficial in each clinical group. In our studies we will include not only ICIs, but also other immunomodulatory drugs and drugs directed against the supportive tumor microenvironment, according to the signatures and cellular targets identified in Aims 2 and 4. We anticipate that the possible combinations may include:
- Antibodies releasing T cell breaks: anti-PD1, anti-PDL1, anti-LAG3, anti-CTLA4
- Small molecules allowing cytotoxic T cell activity: IDO1 inhibitors
- Antibodies activating T cells: anti-OX40, anti-4-1BB, anti-GITR
- Antibodies and small molecules blocking tumor associated macrophages: anti-CSF1R, PLX-3397