Investigating novel therapeutic combinations in pancreatic cancer

A main goal of the Byrne laboratory is to develop improved treatment options for patients with pancreatic cancer. Improved combination chemotherapy approaches have nearly doubled the 5-year survival rate of patients with metastatic pancreatic cancer; however, at only 10%, there is still much work to do on this front. The Byrne Lab has worked on translating agonistic CD40 antibody to the clinical setting in combination with chemotherapy and immune checkpoint blockade, with promising outcomes in Phase I/II trials. Studies are ongoing to address the potential of combining additional therapies to promote enhanced anti-tumor immune responses in patients.

Harnessing CD4 T cell responses against tumors

Historically, immunotherapeutic interventions have focused on enhancing CD8 T cell responses against tumors. However, increasing evidence from the Byrne Lab and others supports the potential of a CD4 T cell-mediated response in rejecting established tumors. We are using a number of genetic and targeted approaches to understand the mechanisms of CD4 T cell immunity against pancreatic cancer, and the potential to further optimize this type of response.

Developing novel models of the pancreatic tumor microenvironment

The complexity of the tumor microenvironment often hinders mechanistic investigations into the underlying immune biology within the tumor site. The Byrne Lab has developed clonal tumor lines that establish unique microenvironments spanning a spectrum of immune phenotypes, allowing for interrogation of mechanisms regulating immune infiltration at baseline or in response to immunotherapy interventions.