Penn investigators say they may have found the Achilles' heel of pancreatic cancer

UPenn's Gregory Beatty

Building on earlier work that demonstrated the promise of anti-CD40 antibodies as a potential new treatment for pancreatic cancer, a science team at the University of Pennsylvania has now illuminated the pathways involved in CD40 therapy in hopes of encouraging investigators in the field to take it into the clinic.

The Penn team found back in 2011 that CD40 therapy could redirect monocytes and macrophages--a subset of cells--to target pancreatic cancer tumors. In this new animal study, they concluded that the CD40 approach worked by opening the door in tumors to macrophages as well as by destroying the fibrotic scaffolding that protects tumors from chemotherapy.

CD40 treatment releases chemokine ligand 2 (CCL2) to assist in the tumor infiltration of macrophages while also boosting interferon gamma (IFNγ), which spurs macrophages to release enzymes that attack the scaffolding.

The anti-CD40 approach can strip a tumor's defenses for about a week, they add, giving a chemotherapy like gemcitabine a better shot at destroying the tumor. And it's better to wait until 5 days after treatment before using the chemo.

Significantly, the researchers saw no evidence that the macrophage approach worked by recruiting T cells for an attack, a popular theory in the oncology world.

"Macrophages can be very potent killers of cancer. Since keeping them out of tumors is a challenge, why not harness their recruitment? This may be the Achilles heel of pancreatic cancer," said Dr. Gregory Beatty, an assistant professor of hematology/oncology at the Perelman School of Medicine at the University of Pennsylvania. "Now that we better understand this biology, we are hopeful that our findings will spark further clinical interest and a path forward to test this treatment approach in patients."

- here's the release

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