La grande évasion: Amélioration de l'activité dans les cellules tumorales de composantes moléculaires transportées via des anticorps conjugués en une technologie de routage intracellulaire avancée

 

Jeffrey Leyton

Université de Sherbrooke

 

Domaine : cancer

Programme chercheurs-boursiers - Junior 2

Concours 2017-2018

Antibody-conjugates (ACs) are a potentially transformative new class of pharmaceuticals for treating and imaging of cancer. ACs contain an antibody used to transport and deliver small molecule payloads within cancer cells. The effectiveness of ACs depend on receptor-mediated endocytosis and trafficking to the lysosome where degradation occurs and the payloads are released. It was thought that this mechanism resulted in efficient accumulation of drugs inside tumor cells that would lead to long-lasting disease-free survival and accurate imaging of tumors. Unfortunately, their effectiveness has been disappointing.

This is because cancer cells are able to effectively redirect the AC and the released payloads back outside the cell. My laboratory recently developed a technology (CellAccumulato [ACCUM]) that allows ACs to escape the entrapments inside the cancer cell that redirect AC and payloads outside the cell. My program saw the potential of ACCUM and strategized for its translation into the clinic to improve the lives of patients with invasive bladder cancer. With external funding and academic and clinical collaborators, my program successfully validated ACCUM. We also obtained a patent for ACCUM. Now with further funding and new industrial collaborators, we aim to further validate and translate ACCUM for the clinic.

My program is divided into four projects that provide 1) a deeper understanding of mechanisms used by ACCUM, 2) to enhance commercial therapeutic ACs, 3) to develop better imaging ACs, 4) perform translational research to develop ACs for invasive bladder cancer.