OnCo
ideasIdea

Drag cancer's surface and secreted proteins to the cell's recycling bin

Some cancer proteins sit on the cell surface or float outside cells, where protein-destroying drugs cannot reach. A different trick can drag them inside to be broken down.

Lysosome-targeting chimeras (LYTACs) and antibody-based equivalents (KineTACs) use receptors such as the cation-independent mannose-6-phosphate receptor or ASGPR to internalise and degrade extracellular and membrane proteins. Cancer targets that resist antibody blockade because they are shed, recycled or in excess (for example growth factors, immunosuppressive ligands, and non-internalising surface antigens) become tractable.

Hypothesis
LYTAC-mediated removal of a shed immunosuppressive ligand from the tumour microenvironment restores T-cell infiltration and improves checkpoint inhibitor efficacy in a syngeneic model more than a blocking antibody alone.
Rationale
Degradation removes protein rather than occupying it, which matters where ligand is continuously produced. The chemistry has been demonstrated for several model targets in cells and mice.
What would test it
Build a LYTAC against one shed ligand with established immunosuppressive function, compare with a blocking antibody in matched syngeneic tumours, and measure ligand levels and T-cell infiltration.
Maturity
preclinical evidence
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
7
Bottlenecks it attacks

Connected

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Pages like this

not linked directly; found by shared links

technologies

2
Monoclonal antibodiesPROTACs & molecular glues (targeted protein degradation)

institutions

1
Stanford Health Care / Stanford Cancer Institute

bottlenecks

2
Cold tumours and the immunosuppressive microenvironmentThe undruggable drivers