Methods and compositions for treating cell senescence accumulation related disease

The inventors have surprisingly demonstrated that GD3 positive senescent cells inhibit NK cell in vitro and in vivo while GD3 negative senescent cells is associated with NK cell functionality, both with human or murine cells. The inventors’ results bring the proof of concept that GD3 expression may represent a Senescence-associated Immune Checkpoint (SIC) that determines senescent cell immunogenicity and identify GD3 and more generally SIC as a multi-hit target for age-associated diseases. Thus, GD3 may be a major step forward in the development of efficient anti-senescence immunotherapies. In particular, the present invention relates to a method for identifying whether a cell is in senescence process comprising the steps of: i) measuring the coexpression level of ST8Sia1 (GD3) with a senescence marker in a biological sample; ii) comparing the co-expression level measured at step i) with its predetermined reference value, and iii) concluding that the cell is in senescence process when the co-expression level of GD3 with a senescence marker is higher than its predetermined reference value or concluding that cell is not in senescence process when the co-expression level of GD3 with a senescence marker is lower or similar than its predetermined reference value. The present invention also relates a method for treating senescent cells accumulation related disease in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a GD3 inhibitor.

Keywords: Senescence, IPF
Publications:
https://doi.org/10.1101/2021.04.23.440408

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