Towards the rational design of cancer therapies combining tumorderived dendritic cell vaccinations with regulatory T

Project Details

Description

Breast and lung cancer are among the cancers with the highest
incidence and mortality. Unfortunately, the response rate to immune
checkpoint inhibitors is low in both cancer types, indicating that
tackling one aspect of the immune system is insufficient to induce a
successful anti-cancer immune response. Recently, my host lab
developed two novel treatment strategies currently in a pre-clinical
stage in preparation of a clinical trial: (1) vaccination with tumorderived conventional dendritic cells (cDCs) and (2) targeting
immunosuppressive tumor-Tregs using anti-CCR8 constructs. This
project aims to provide first proof-of-concept for the rationally
designed combination of both treatments. To do so, I will perform
scRNAseq and spatial transcriptomics on murine tumors upon
treatment with anti-CD25 antibodies or anti-CCR8 constructs to
unravel how different Treg populations influence the molecular
phenotype of distinct cDC subsets in the tumor. Further in-depth
analysis using functional assays and 3D spheroids with sorted Treg
and DC subsets will allow to identify which cDC subset should be
used as vaccine in combination with one of the Treg targeting
therapies. I will evaluate the efficacy of these combinations in murine
breast and lung cancer models and in a novel mouse metastatic lung
cancer model to confirm the therapeutic potential of these novel
combination treatments. Therefore, my project will pave the path
towards evaluation of these combinations in a clinical setting.
AcronymFWOSB136
StatusActive
Effective start/end date1/11/2231/10/26

Keywords

  • Novel combination treatments against cancer
  • Treg targeting and cDC vaccination therapies
  • Evaluating the Treg and DC interplay in the tumor

Flemish discipline codes in use since 2023

  • Cancer biology
  • Innate immunity
  • Adaptive immunology
  • Cancer therapy
  • Applied immunology

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