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

VaccineFrameshiftCancerExploratoryPreclinicalPhase IPhase II

MSI cancer
Lynch Syndrome1

New candidatesundisclosed
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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)
[1] Sæterdal I, Bjørheim J, et al, Proc Natl Acad Sci USA. 2001 Nov 6;98(23):13255-60. Sæterdal I, Gjertsen MK et al, Cancer Immunol Immunother 2001; 50: 469-476.

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

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