A couple of high-profile cancer researchers at MD Anderson backed by the Parker Institute have been exploring an experimental pathway that they believe shows some real potential in treating pancreatic cancer. And the news could buoy developers beavering away at clinical development in this arena of immunotherapy.
Padmanee Sharma along with her longtime collaborator, husband and Nobel laureate Jim Allison approached the issue by comparing pancreatic cancer tumors against melanoma, where PD-1/L1 and CTLA-4 checkpoint inhibitors have showed some of their greatest successes. Pancreatic cancer, though, has a small 5-year survival rate, demonstrating its resistance to the new checkpoint class of drugs now out on the market.
Sharma and Allison’s team noted a significantly different profile for each cancer, with a much higher level of stroma in pancreatic cancer tumors that could be interfering with existing checkpoints. The stroma — supportive cells — is layered into pancreatic cancer.
“In melanoma, you have a large area of malignant cells surrounded by a thin layer of stroma,” noted Sharma. “With pancreatic cancer, it’s more like cancer cells, stroma, cancer cells, stroma ― blended.”
The investigators also noted a higher expression of VISTA — V-domain Ig suppressor of T cell activation — in pancreatic cancer.
Allison’s observation is that stroma may in turn keep T cells out of the pancreatic cancer tumors. The cancer scientist won the Nobel prize in medicine for his original work on the CTLA-4 checkpoint, which opened the door to an immense amount of work globally following it up with new approaches.
There are several VISTA antibodies in the global pipeline, they note. That group evidently includes Curis, a penny stock microcap which has a small molecule program that combines VISTA and PD-L1.
The goal now, the MD Anderson pair sum up, is to see about starting work on some new checkpoint combos — perhaps matching CTLA-4 and VISTA. Their work was funded by Pancreatic Cancer Moon Shot, a grant from the National Cancer Institute and the Parker Institute for Cancer Immunotherapy.
Image: Jim Allison and Padmanee Sharma at the King’s dinner for the Nobel Laureates. AP IMAGES
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