Defining a novel immunotherapy for more effective cancer treatment

Lead researcher

Dr Florian Wiede

Dr Florian Wiede

Institution

Monash University

Tumour type:

Bowel, Breast, Lung, Lymphoma and Melanoma

Years funded

2016-2018

Project description

The immune system is a complex network of cells that allows the human body to battle infectious diseases, suppress autoimmune disorders or combat the development of cancer. Cytotoxic T cells, a subset of specialised immune cells, play a critical role in the killing of tumour cells. However, tumours develop complex inhibitory mechanisms that can ‘silence' cytotoxic T cells, thereby allowing for tumor growth and dissemination.

We have recently identified the protein PTPN2 as a key regulator of cytotoxic T cells and we could show that PTPN2 prevents cytotoxic T cells from killing tumour cells. We will explore whether the inhibition of PTPN2 might enhance the T cell's ability to attack and kill tumour cells.

What is the need?

The inability of the immune system to initiate a robust anti-tumour response is often linked to poor prognosis for patients with solid tumours including advanced melanomas, breast, renal and ovarian cancers. In particular, tumours can express molecules such as PD-1 ligand and CTLA-4 that effectively ‘silence' anti-tumour T cells.

While therapies involving the administration of drugs to boost tumour-specific T cell responses have delivered promising results in the clinic, the ongoing search for novel targets to further improve cancer therapy is critical.

What is the impact of this research?

Our work will shed light into mechanisms that contribute to cytoxic T cell exhaustion and the non-responsiveness of the immune system to tumour cells. It will also help to further improve existing therapies using drugs that are directed against PD-1 ligand and CTLA-4.

By targeting molecules that prevent a robust tumourspecific T cell response, we will define a novel immunotherapy for a more effective cancer treatment.

Project timeline

2016  2017 
2018 

Found PTPN2-deficient tumour-specific CAR T cells exhibit increased tumourspecific activation and enhanced tumour killing.

Transferred tumour-specific PTPN2-deficient CAR T cells into tumour bearing mice and monitored tumour growth and survival. We found an increased survival of the mice that had received these T cells.

 
Determine whether PTPN2- deficiency in CAR T cells cooperates with PD-1 blockade to further enhance anti-tumour responses. Focus on establishing knockdown and inhibition strategies for PTPN2 in CAR T cells to enhance the response.  

"By targeting molecules that prevent a robust tumour-specific T cell response, we will define a novel immunotherapy for a more effective cancer treatment."