HLA-G as a new target for immune checkpoint inhibitors for cancer immunotherapy

Through this project it was investigated whether it was possible to develop a peptide that can bind to HLA-G; a protein that does not occur in normal circumstances but is present in 25% of the tumors and is an interesting target for therapy and imaging of cancer.  

Cancer has a high societal and economic impact as the number 1 cause of death in the Western world. Considering the presence of HLA-G on tumors as well as its role in (the progression of) cancer, developing HLA-G-binding peptides can eventually be used for cancer imaging and immunotherapy. Therefore, this is a promising line of research that may affect thousands of cancer patients yearly.  First, they selected and synthesized a number of peptides theoretically capable of binding to HLA-G and aimed to show their binding to the HLA-G protein and HLA-G on living (tumor) cells. All peptides were found to bind well to the HLA-G protein. Next, they wanted to demonstrate that the peptides could also bind to HLA-G on living cells. After synthesis of several peptides and lengthy optimization steps, evidence that the peptides bound to HLA-G on living cells was unfortunately not found. Then, they designed a new peptide variant that contained a fluorescent dye, making it easier to detect. It seemed that this peptide could bind to HLA-G on live cells.

In parallel with the above, this project has published two scientific review articles in leading journals to indirectly prompting new research on HLA-G. Additionally, they have, for the first time, evaluated the presence of HLA-G on metastatic gastric cancer and demonstrated that HLA-G is heavily present on these tissues. The project provided the consortium with crucial knowledge and experience on HLA-G and the development of HLA-G-binding peptides, thereby laying the foundation for further work into this promising topic and, potentially, a novel treatment strategy for thousands of cancer patients yearly.