Peptide Vaccination Against Cancer Testis Antigens in Combination With Azacitidine for Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia: an ongoing phase I study

Myelodysplastic Syndrome (MDS) is a clonal disorder and characterized by increasing bone marrow failure due to accumulation of genetic and epigenetic changes in hematopoietic stem cells. Patients with high-risk disease have a poor prognosis and a high risk of progression to Acute Myeloid Leukemia (AML).

The dysplastic cells harbor chromosomal breakage, point mutations and promoter hyper-methylation of tumor suppressor genes.For most patients, who are not eligible for bone marrow transplantation, hypomethylating agents, such as azacitidine (AZA), are currently the only treatment option. The demand for more effective therapies in this patient group is huge.

Though the mechanism of AZA is not fully elucidated re-expression of tumor suppressor genes can serve as a mechanism for growth arrest. In addition, there is accumulating evidence for an up-regulation of cancer testis antigens (CTA), which could lead to increased immune recognition of tumor cells and immune-mediated tumor cell killing.

CTA’s are known to be immunogenic and are only expressed at immunoprivileged sites and on malignant cells, making them attractive as targets for therapeutic cancer vaccination.