IPPON preclinically and clinically investigates combining immune stimulation with immune checkpoint blockade to further boost the antitumor immunity by acting on different phases of the cancer immunity cycle. Per tumor type different approaches are chosen.
To study immune activation, different strategies are investigated for their ability to induce so-called immunogenic cell death, a form of cell death that results in immune activation. These strategies include the use of
- chemotherapeutic agents
- targeted therapy
- radiotherapy
- cold atmospheric plasma
- These cell death pathways are studied, using (epi)genetics, (epi)transcriptomics and proteomics.
Other immune activators that are investigated by IPPON, include
- dendritic cell vaccination
- Toll-like receptor ligands
- interleukin 15
- CD40
To improve current clinical results, IPPON preclinically and clinically investigates the effect of targeting new inhibitory immune checkpoints, by using blocking antibodies or chimeric antigen receptor (CAR) NK cells. These immune checkpoint inhibitors include TIM-3, LAG-3 and CD70.
Other factors contributing to the immunosuppressive environment of the tumor are also being investigated by IPPON. These mechanisms include
- cancer-associated fibroblasts
- hypoxia
- receptor activator of nuclear factor k B (RANK)
By characterizing the tumor microenvironment, we can identify suitable targets for immunotherapy and investigate the therapeutic effect of targeting these molecules preclinically and clinically.