Blocking `Don`t Eat Me` Protein Has Potential in Pancreas Cancer
By Megan Brooks
NEW YORK - Blocking the protein CD47, which is elevated on pancreatic neuroendocrine tumor cells and pancreatic ductal adenocarcinoma cells, causes tumor regression in preclinical models of both cancers, according to new research presented this week at the American Association for Cancer Research's special conference, Pancreatic Cancer: Innovations in Research and Treatment, in New Orleans.
"CD47 is a cell-surface protein that functions as a 'don't-eat-me' signal that allows cancer cells to evade immune surveillance," Dr. Geoffrey W. Krampitz of Stanford University School of Medicine in California, explained at a press briefing. "When CD47 is blocked from interacting with its receptor, pro-phagocytic signals dominate resulting in phagocytosis of the cancer cell, leading to inhibition or elimination of primary tumors and metastases."
Dr. Krampitz and colleagues analyzed tumor samples from patients with pancreatic neuroendocrine tumors and pancreatic ductal adenocarcinoma. They found that CD47 is expressed at elevated levels on the cells that make up "the bulk of the tumors and on the tumor-initiating cells, which are the cells that propagate disease and cause metastasis," Dr. Krampitz said in a conference statement.
The researchers also found that blocking CD47 function with a monoclonal antibody had antitumor activity in a number of different preclinical models of these pancreatic cancer types. In one model, in which mice were transplanted with tumors from patients with pancreatic neuroendocrine tumors or pancreatic ductal adenocarcinoma, treatment with a CD47-blocking monoclonal antibody caused marked tumor regression.
In their ongoing studies, Dr. Krampitz said he and his colleagues have also shown that blocking CD47 with monoclonal antibodies and other agents can "dramatically enhance the efficacy of cancer-targeting immunotherapies including rituximab for lymphoma and trastuzumab for breast cancer."
"In addition, we have shown that anti-CD47 antibody treatment selectively increases the ability of macrophages to prime and activate cytotoxic T-lymphocytes, which may limit tumor growth, beyond the time of anti-CD47 monoclonal antibody treatment," Dr. Krampitz told the briefing.
"We have amassed a large amount of preclinical data indicating that blocking CD47 signals unmasks cancer cells and allows the immune system to recognize and destroy tumor cells," he added.
"We are optimistic that targeting CD47 in this way could provide a new approach for treating patients with pancreatic cancer who have a desperate need for improved treatment options," Dr. Krampitz said.
This study was supported by funds from the Virginia and D.K. Ludwig Foundation for Cancer Research, the National Cancer Institute, the A. P. Giannini Foundation, the Siebel Stem Cell Institute and the Thomas and Stacey Siebel Foundation, an Anonymous Donors Fund, and the American College of Surgeons. Dr. Krampitz has declared no conflicts of interest.
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