Target mutations and vaccines
By focusing on the most common and shared frameshift mutations across MSI cancers Hubro Therapeutics has established a proprietary neo-peptide technology platform. The core neoantigens of the proprietary technology platform cover frameshift mutation in TGFβR2, , ASTE1 and TAF1B. Additional targets are being explored.
The neo-peptide technology platform provides a solid basis for development of both single-target vaccines and multi-target vaccines.
Targeting shared neo-antigens in MSI-cancer
| Vaccine | Frameshift | Cancer | Exploratory | Preclinical | Phase I | Phase II |
|---|---|---|---|---|---|---|
| FMPV-1 | TGFβR2 | Colorectal Gastric | ||||
| FMPV-2 | TGFbR2 HT001 TAF1B | MSI cancer Lynch Syndrome1 | ||||
| New candidates | undisclosed | |||||
Targeting shared neo-antigens in MSI-cancer
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Lead candidate vaccine FMPV-1
The lead vaccine candidate FMPV-1 targets frameshift mutation in the transforming growth factor β receptor 2 gene (TGFβR2). Frameshift mutant TGFβR2 is present in 44% of MSI related cancers and particularly in more than 77% of MSI-H colorectal cancer and 80% of MSI-H gastric cancer. Over 90% of patients with familial hereditary colorectal cancer have TGFβR2 frameshift mutation.
- TGFβR2 frameshift is a potential driver mutation for malignant transformation
- Interaction between TGFβR2 and TGFβ mediates control of cell growth
- Mutant TGFβR2 is biologically non-functional and induces escape from growth control leading to cancer progression
- mutTGFbR2 neo-peptides are immunogenic in cancer patients [1]
- Has a potential as a prophylactic vaccine
- Would be of value in Lynch Syndrome where there is a 55-80% risk of early onset of colon cancer (mean age of onset 44-61 years)
fsp2: 24 amino acid designed neo-peptide
Fsp5: 33 amino acid target neo-antigen (TGFβR2) peptide
Tc: T cells,
APC: antigen presenting cell
PBMC: Peripheral blood mononuclear cell
SI: Stimulation index