PhD thesis of Alexandra Barthelemy (Conjugated bispecific antibody formats for targeted therapy of TNBC)

Summary

In this thesis project, we propose to study, the relevance of bispecific FDCs targeting 2 tumor antigens in TNBC: TROP-2 and HER3. Indeed, binding to two different targets on the same cell makes it possible to increase the specificity of the drug, which will also help reduce off-target side effects. Thus, several formats of conjugable antibodies will be constructed, produced and characterized. These different formats will then be bioconjugated with deruxtecan linker to produce FDCs with a DAR of 4. These armed bispecific antibody formats will then be tested on 2D and 3D TNBC cellular models (including or not fibroblasts). The best of the formats will be tested in vivo on a xenograft model in mice and according to an administration schedule which remains to be defined depending on the chosen format.