Fut8: Sugar-coating immuno-oncology

Fut8: Sugar-coating immuno-oncology

The opportunity

  • Curative or durable treatments for advanced and metastatic cancers are needed 
  • Fut8 inhibition reduces cancer spread by modifying tumour and T cell phenotypes
  • Screening program initiated and unique pre-clinical models developed

Blocking antibodies against programmed cell death protein 1 (PD-1) are rapidly becoming the standard of care for advanced cancers.

Responses to immuno-oncology drugs such as anti-PD-1 vary dramatically between cancer types, and while they can offer a survival benefit, durable responses are still rare.

Identifying new mechanisms and therapeutic targets that synergise with PD-1 inhibition are crucial to improving patient survival.

The technology

Fut8 is the only fucosyltransferase enzyme that fucosylates the core of N-glycans.

Blocking core fucosylation has a dual role in suppressing tumour progression by (1) improving the anti-tumour immune response and (2) reducing the cancer’s intrinsic metastatic potential:

  1. Blocking FUT8 reduces expression of PD-1 and promotes T-cell anti-tumour activity
  2. Blocking FUT8 alters L1CAM cleavage and reduces cell invasion and metastasis

Scientific diagram  Scientific diagram

Opportunities for partnership 

We are using a structure enabled drug design approach to synthesise first-in-class molecules that selectively inhibit FUT8.

We have:

  • structures of FUT8 with and without ligands bounds in the active site
  • a validated assay suitable for high-throughput screens
  • preliminary lead-like and fragment screening data
  • pre-clinical mouse models (knockout and conditional knockout of FUT8)

We are seeking:

  • Investment to enable us to complete medicinal chemistry and preclinical testing

Scientific team

Dr Ethan Goddard-Borger, Laboratory Head, Chemical Biology Division

Contact

Dr Anne-Laure Puaux, Head, Commercialisation

Phone: +61 3 9345 2175 

Email: partnering@wehi.edu.au