Therapeutic Vaccine MSI – MicOryx

 

Description

Several cancers arise from the lack of DNA mismatch repair (MMR) resulting in the accumulation of thousands of single deletions or insertions at coding microsatellites (MSI-H). These mutations lead to the inactivation of specific proteins and to the expression of frameshift peptides (FSPs). These FSPs are tumor-specific antigens, which are constantly expressed.

Cancers with MSI-H mutations include 10-15 % of colorectal cancers, 20-25 % of endometrial cancers, 25-30 % of upper urinary tract cancers, 15-20 % of intestinal gastric cancers and 5-10% of pancreatic cancers.

In patients with MSI-H colorectal cancer, humoral and cellular immune responses against FSPs occur spontaneously. In healthy people, such immune responses have not been observed.

Mode of Action

The observation that FSP expression triggers specific immune reactions in patients is the basis of the vaccination approach with therapeutic vaccine MSI using a cocktail of three synthetic FSPs, AIM2(-1), HT001(-1) and TAF1B(-1) to prevent outgrowth or to destroy MSI-H tumors.

More information on the collaboration with the German Cancer Research Center (DKFZ)

MicOryx Trial

The clinical development of MicOryx started in Q4/2011. The Phase I/IIa trial was designed to immunize patients with MSI-H positive colorectal cancer using therapeutic vaccine MSI. This prospective two part open-label trial was conducted at single center and successfully completed in Q1/2015.

Primary objective of the Phase I part was safety. Secondary objectives were immune response against therapeutic vaccine MSI and tumor response.

Primary objective of the Phase IIa part was immune response against therapeutic vaccine MSI. Secondary objectives were safety and tumor response.

Results: The vaccine was safe, showed strong immune responses against FSPs, plus strongly induced T cell (mainly CD4-positive) and humoral immune responses in all patients vaccinated. No frameshift peptide (FSP) antigen-associated severe adverse events were observed. Full data were presented at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO).

For more information see: ClinicalTrials.gov