Exploring the mechanisms of RESponse and RESistance to novel Cancer immunotherapies in tumors Unresponsive to Earlier immune checkpoint inhibition

Project Details


Immunotherapy has moved from a topic of preclinical investigation to a therapy that has changed the way
many cancer patients are managed. Vast clinical efforts have been dedicated to advancing treatment with PD-
(L)1 and CTLA-4 immune checkpoint blocking antibodies. Unfortunately, the majority of solid tumors are
resistant to these therapeutics, and the mechanisms of resistance require elucidation. The RESCUE-project
will take advantage of unique patient materials obtained from ongoing academia sponsored clinical trials where
patients, refractory to PD-(L)1 blockade, receive intratumoral injection of myeloid dendritic cells that stimulate
adaptive immunity together with immune adjuvants. Tumor tissues, immune cells isolated from tumors,
cerebrospinal fluid and peripheral blood are collected at baseline and on-treatment from responding and non-
responding patients. These will be evaluated using genome analysis, gene expression profiling, and multiplex
immunofluorescence to gain insight into mechanisms of response and resistance. Tumor directed T-cell
receptors of responding patients and resistance markers, such as B7-H3 (already identified as a resistance
mechanism in an ongoing study for glioblastoma patients), will serve for designing clinically applicable novel
chimeric antigen receptor therapies. These, after validation using patient-derived tumor cells, could be used to
rescue patients affected by tumors that are refractory to PD-(L)1 blockade as a monotherapy
Effective start/end date1/01/2231/12/25


  • CTLA-4
  • Myeloid dendritic cells
  • CAR-T cells
  • T-cell receptor
  • multiplex immunohistochemistry
  • immune checkpoint
  • B7-H3
  • PD-1
  • PD- L1

Flemish discipline codes in use since 2023

  • Cancer biology
  • Adaptive immunology
  • Cancer therapy
  • Applied immunology


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