Active Cancer Infection & Immunity

PhD Grant Application: Interactions between IL-18-armoured NKG2D CAR T Cells and the Triple Negative Breast Cancer Microenvironment

Funder Wellcome Charity-funded
Recipient organisation King's College London
Funding Not disclosed
Period Oct 2025 — Sept 2028

In plain English

AI plain-English summary

A patient’s own immune cells are being engineered to attack triple-negative breast cancer, but the tumour’s defences keep shutting them down. Triple-negative breast cancer has few treatment options and a poor outlook. CAR T-cell therapy—where a patient’s T cells are reprogrammed to recognise and kill cancer cells—works in mice with weakened immune systems, but fails in real patients because the tumour microenvironment actively suppresses the immune attack. This PhD project aims to understand exactly how that suppression happens, and whether a specific type of CAR T cell, armed with an inflammatory molecule called IL-18, can flip the tumour’s defences into an immune-friendly state. If successful, the research could reveal a general strategy for making CAR T-cell therapy effective against solid tumours, not just blood cancers. That would open a new treatment path for thousands of patients with triple-negative breast cancer and potentially other hard-to-treat solid tumours. The work is fundamental science—it will not produce a therapy tomorrow—but it will provide the mechanistic understanding needed to design smarter, more resilient cell therapies that can survive and thrive inside a hostile tumour.

View original technical description
Triple-negative breast cancer (TNBC) has poor prognosis due to few treatment options. CAR T-cell therapies, which redirect T cells to target tumours, show efficacy in immunodeficient mouse models of TNBC, but clinical benefits remain limited. A major barrier to efficacy is the immunosuppressive tumour microenvironment (TME). This PhD will investigate how murine NKG2D-based CAR (mLEU011) T cells remodel the TNBC TME in immunocompetent mice. I hypothesise that mLEU011 will shift the TME from immunosuppressive to immunoreactive by targeting NKG2D ligand-expressing immunosuppressive cells, and by activating endogenous immunity via epitope spreading. I predict that armouring mLEU011 CAR T cells with the pro-inflammatory cytokine IL-18 will enhance these immunoreactivating effects. To test this, I will generate IL-18-armoured mLEU011 CAR T cells, validate their function in vitro, and assess safety in vivo. In parallel, I will establish a syngeneic mouse model of TNBC to evaluate CAR T-cell efficacy and profile TME changes and host immune activation. Changes in the TME will be analysed using flow cytometry, multiplex immunohistochemistry (mIHC), and spatial transcriptomics. This project will provide mechanistic insights into CAR T-cell-mediated remodelling of the TNBC TME and inform the development of new CAR T-cell therapies for TNBC and other solid tumours.

View the original record at the funder ↗

Researchers

Paulina Vicenova (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

MICA: Optimising combination strategies for chimeric antigen receptor therapy in multiple myeloma
Manipulating myeloid cells to improve cancer immunotherapy
Characterization of the immune microenvironment present in murine models of triple-negative breast cancer
TIL Recruitment and Activation in Triple Negative Breast Cancer
Manipulating the Tumour Microenvironment to Optimise TIL therapy

Original classification

PhD Studentship (Basic)

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.