Pseudovax - A Cancer Vaccine for Patients With Pseudomyxoma Peritonei

Pseudomyxoma peritonei (PMP) is a rare, slow-growing abdominal cancer that commonly originates in ruptured appendiceal mucinous neoplasms, which seed tumor cells and mucin into the peritoneal cavity. The disease is characterized by slow, progressive growth and accumulation of mucinous tumor tissue in the peritoneal cavity, ultimately leading to abdominal compression and death. Standard-of-care treatment (SOC) involves extensive cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC), and is curative in approximately 50% of the patients, but for patients who cannot be cured by SOC, no efficacious treatment options exist. In the setting of non-resectable and recurrent disease, PMP is a debilitating and ultimately fatal condition, leaving patients to experience progressively poor quality of life caused by an increasing intraperitoneal tumor burden. In research carried out by the study team, mutated GNAS as a potential tumor neo-antigen was investigated by analyzing tumor and peripheral blood samples collected from PMP patients at the time of surgery.

The results (detailed in the Pseudovax IB) indicated that the patients had a strong immune response against mutated GNAS. However, the presence of a high tumor burden at the time of surgery implies that the immune response had been insufficient to control tumor growth. Further analyses revealed that this could be explained by inhibition of anti-tumor T cells by up-regulation of immune checkpoint molecules.

These results provide the rationale for vaccination targeting mutated GNAS to increase the number of tumor cell targeting T cells. Furthermore, the observed up-regulation of programmed death-1 (PD-1) on intratumoral T cells provides rationale for combining the vaccination with a PD-1 inhibitor. Importantly, very few patients with PMP have had the opportunity to test treatment with immune checkpoint inhibitors. The main reason is that PMP molecularly is a microsatellite stable disease with very low tumor mutational burden, and patients are therefore not likely to respond to immune-check point inhibition (ICI) monotherapy. The planned combination with the Pseudovax peptide vaccine may represent a unique opportunity to derive benefit from ICI treatment for this patient group.