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Blocking CD47 Signals May Offer New Therapeutic Approach in the Treatment of Pancreatic Cancer

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Key Points

  • Two preclinical studies 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 for both pancreatic neuroendocrine tumors and pancreatic ductal adenocarcinoma.
  • Using the monoclonal antibody Hu5F9, which blocks CD47 signals, caused tumor regression in both pancreatic neuroendocrine tumor cells and pancreatic ductal adenocarcinoma cells.
  • 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.

Two preclinical studies of tumor samples taken from 39 patients with pancreatic neuroendocrine tumors and 39 patients with pancreatic ductal adenocarcinoma has found that for both these pancreatic cancers, CD47 is expressed at elevated levels on the cells that make up the bulk of the tumors and on the tumor-initiating cells. The researchers also found that using the monoclonal antibody Hu5F9, which blocks CD47 signals, caused tumor regression in both types of pancreatic cancer. The research by Krampitz et al was presented at the American Association for Cancer Research (AACR) conference on Pancreatic Cancer: Innovation in Research and Treatment, held in New Orleans on May 18 to 21.

Study Findings

The researchers tested the effects of blocking CD47 function in a number of different preclinical models of pancreatic neuroendocrine tumors and pancreatic ductal adenocarcinoma. Antitumor activity was observed in each model. In one model, in which tumors from either patients with pancreatic neuroendocrine tumors or those with pancreatic ductal adenocarcinoma were transplanted into mice, treatment with a monoclonal antibody that recognizes and attaches to CD47 and blocks its function caused dramatic tumor regression.

“CD47 is a widely expressed cell surface protein that functions as a ‘don’t eat me’ signal,” said Geoffrey Krampitz, MD, lead author of the studies and a doctoral candidate in the laboratory of Irving L. Weissman, MD, Director of the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University School of Medicine and the Ludwig Center for Cancer Stem Cell Research at Stanford, at a press conference announcing results of the studies.

“We have shown that blocking CD47 with monoclonal antibodies and other agents can dramatically enhance the efficacy of cancer-targeting immunotherapies, including rituximab [Rituxan] for lymphoma and trastuzumab [Herceptin] 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. We have amassed a large amount of preclinical data that indicates that blocking CD47 signals unmasks cancer cells and allows the immune system to recognize and destroy tumor cells,” he said. 

The study was funded by 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 Donor Fund, and the American College of Surgeons. Dr. Krampitz reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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