Evaluating the anti-tumor potential of PARP inhibitor treatment in combination with dendritic cell-based therapies in triple negative breast cancer

Project Details

Description

Treatment options for aggressive triple negative breast cancer (TNBC) are still limited. Only patients with
germline BRCA1/2 mutations can currently benefit from targeted therapy with PARP inhibitors (PARPi).
However, even these patients relapse and hence combination strategies with PARPi are being investigated in
patients with and without BRCA1/2 mutations. One strategy to increase the response to PARPi is to improve the
anti-tumor immune response. Dendritic cells are at the forefront when mounting an anti-tumor immune response.
Therefore, the goal of the current project is to evaluate the anti-tumor potential of combining PARPi treatment
and DC-based therapies. Using CITE-seq, flow cytometry and functional assays, we first characterize the DC
compartment in models of BRCA1 or BRCA2 deficient TNBC upon PARPi treatment. Then, by depleting DCs
from the tumor using genetic models or by increasing their influx/activation in the tumor by combining PARPi
with cDC cell therapy, CD40 agonist or Flt3L therapy, we will respectively establish if DCs are required for
PARPi response and if enhancing DCs can increase the response to PARPi in TNBC. Overall, this project will
therefore significantly improve the understanding on the impact of PARPi on tumor-DCs as well as uncover
novel combination strategies for treatment of BRCA proficient or deficient TNBC.
AcronymANI360
StatusActive
Effective start/end date1/11/2331/10/24

Keywords

  • PARP inhibitor
  • dendritic cell-based

Flemish discipline codes in use since 2023

  • Cancer therapy

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