The Pseudovax project
Research challenge: Pseudomyxoma peritonei (PMP) is an extremely rare, slow-growing abdominal cancer that originates in tumors of the appendix that rupture and disseminate to the peritoneal cavity. Surgery cures half of the patients, but there are no efficacious treatment options in non-resectable and recurrent cases.
Our research: (Flatmark/Inderberg J ImmunoTher Cancer, 2021, PMID 34711663)
Unique mutational driver: Otherwise rare single-nucleotide mutations in the GNAS oncogene (coding for Gsα) are detected in up to 90% of PMP cases.
Mutated Gsα – a cancer neo-antigen: Strong T cell proliferative response against Gsα mutated peptides in PMP patients. Infiltration of T cells expressing PD-1 and TIGIT immune checkpoint molecules in most tumor samples, indicating antigen-experienced T cells.
Conclusions: The immune response in PMP patients towards mutated Gsα has been insufficient to control tumor growth, possibly because of inhibition of anti-tumor T-cells by up-regulation of immune checkpoint molecules. The results support exploring peptide vaccination with Gsα peptides in combination with immune checkpoint inhibition as a possible curative treatment for PMP and other GNAS mutated cancers.
This concept will be explored in the Pseudovax first-in-man trial (see clinical study synopsis):
