New Class Of mUlti-taRgeted Antibody druG conjugatEs – COURAGE

Cancer still constitutes major public health around the world. Developing new treatments belonging to the class of targeted therapies, such as therapeutic antibodies (Abs), is highly recommended to improve cancer patients' care. However, the overall clinical efficacy of naked antibodies remains limited, especially in monotherapy and in the treatment of solid tumors. To increase the therapeutic potential of naked Abs, conjugation to potent cytotoxic molecules to form Antibody-Drug Conjugates (ADCs) was developed, and improved their efficiency spectacularly.
ADCs can selectively destroy malignant cells while sparing healthy tissue. However, current ADC treatments still induce adverse effects due to a combination of a lack of stability (retro-Michael reactions) and a high level of heterogeneity limiting their therapeutic window.
This project's main objective is to develop next-generation ADCs with novel payloads (dual mechanism of action), which are highly homogeneous and stable and widen their therapeutic window.
To this end, our project is based on two complementary technologies:
- original payloads developed in the CoSMIT laboratory with high antiproliferative activity (nM-picoM), metabolic stability, and with a functional group that will allow the anchoring point with the linker. Furthermore, these payloads present original mechanisms of action as anti-tubulin and histone deacetylases inhibitors, which allow for maintaining activities against resistant tumor cells.
- McSAF Inside bioconjugation technology which will optimally control the payload's stoichiometry, stability, and release to lead to better activity and tolerance of the ADC.
This project's ambitious and innovative character is based on developing new ADCs, which present original mechanisms of action with perfect control of the release at the target level of the tumor cells.