Improving immunotherapy for pancreatic cancer

Improving immunotherapy in solid tumors

Attacking the outer layer of a pancreatic tumor to make way for immunotherapy.

In the Netherlands, 3,500 patients are diagnosed with pancreatic cancer per year. Only 20% of these patients survives for more than 12 months after diagnosis, even when aggressive treatments are applied, because in many cases the disease has already spread by the time it is diagnosed. There is an urgent need of new treatments that have a meaningful impact on the survival and quality of life of these patients.

Immunotherapy is such a new treatment option. The goal of this form of therapy is to activate the immune system of a patient to fight against the tumor. Current forms of immunotherapy appear not to be effective for pancreatic cancer. This is because pancreatic tumors and its metastases build kind of a wall around themselves, which prevents immune cells from reaching the tumor itself. This consortium has developed a strategy to counteract this effect, to make the tumor and potential metastases susceptible for immunotherapy. For another form of cancer, we have successfully developed a novel form of immunotherapy: dendritic cell immunotherapy. In this project, this dendritic cell immunotherapy will be combined with a compound that attacks the walls. We aim to demonstrate that this combination makes dendritic cell immunotherapy effective for treatment of pancreatic cancer in a mouse model.

We have found pancreatic cancer and mesothelioma lysate-loaded DCs to be effective in restraining immunologically cold pancreatic tumors when administered prophylactically. In established tumors, effective intratumoral immunity was achieved when DC vaccination was combined with CD40-agonistic antibodies, generating non-redundant immunological effects capable of restraining tumor progression.

Taken together the results obtained within this project demonstrate the potency of DC therapy in combination with CD40 stimulation for the treatment of pancreatic cancer and provide directions for near future clinical trials.

Summary
Pancreatic tumors and their metastases shield themselves from the immune system by building walls around themselves. We want to break down these walls and combine this with immunotherapy to enable the immune system to attack the tumors.
Technology Readiness Level (TRL)
3 - 7
Time period
36 months
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