Beurs Emmanuel Van der Schueren: The Trojan Horse: an old strategy coming of age to explore and defeat tumors from within

Project Details

Description

A solid tumor can be seen as a fortress that protects its cancer cells from immune surveillance. Key players within this fortress are the tumor infiltrating myeloid cells (TIMs), which form a heterogenous group that can promote or decrease tumor growth, depending on their differentiation state. Since it is difficult to reach these cells systemically, we propose to develop a ‘Trojan Horse’, based on the in situ genetic modification of cancer cells to turn them
into permanent ‘Nanofactories’, which produce TIM-targeted nanobody (Nb) fusion proteins.
As such we hope to answer the following fundamental questions: (1) which TIM-targeting Nbs are suitable to target specific TIM subsets and (2) which TIM subtypes have to be depleted and/or modulated to provide substantial therapeutic benefit. Practically we want to develop lentivectors (LVs) encoding Nb-fusion proteins that turn tumor cells into Nanofactories upon their intratumoral delivery. To study TIM-targeting, we will inject LVs that encode fluorescently labeled Nbs against different TIM subtypes to determine both selective targeting and internalization. Next we will study the immunological and therapeutic effect of LVs encoding Nbs fused to a pro-apoptotic or signal transducing protein to deplete or modulate different TIM subtypes in different tumor models.
In sum we want to develop an approach to explore solid tumors from within. If successful, this approach holds promise for the design of unique targeted antitumor immunotherapeutics.
AcronymANI160
StatusFinished
Effective start/end date1/10/1630/09/19

Keywords

  • tumor infiltrating myeloid cells