Promising results from an early-stage clinical trial may lead to new treatment options for patients with advanced pancreatic cancer. The treatment appears to work differently than the trial investigators had expected, attacking tumors primarily by altering their surrounding tissue. The findings were published online March 25 in Science.
The phase I clinical trial, funded by Pfizer, involved 21 patients newly diagnosed with advanced pancreatic cancer, for whom current therapies are mostly ineffective and 5-year survival rates are less than 5 percent. Patients received the chemotherapy drug gemcitabine and a monoclonal antibody called CP-870,893 that binds to the CD40 receptor on the surface of certain immune cells.
Overall, four patients had some tumor shrinkage (partial response) and 11 saw their disease stabilize, with no further tumor growth. The median progression-free survival was 5.6 months and overall survival was 7.4 months, both of which are superior to what is historically seen in patients treated with the current standard of care, gemcitabine alone, explained the study’s lead investigator, Dr. Robert Vonderheide of the University of Pennsylvania’s Abramson Cancer Center.
The researchers expected the CD40 antibody to stimulate T cells to attack the tumor, but an analysis of tumor samples from two patients whose tumors responded to therapy found few or no T cells. The researchers did find an abundance of another type of immune cell, macrophages, which typically have been thought to help tumors ward off assault by the immune system.
To help determine what may be happening in these patients, the researchers treated mice that were genetically engineered to develop pancreatic cancer with a similar CD40-targeted antibody. This antibody was found to bind to macrophages outside of the tumor, Dr. Vonderheide noted. Consequently, he added, the macrophages “changed their properties, took on killing properties, and quickly migrated to the tumor.” In the mice, he continued, “we saw the death of tumor cells themselves, but we also saw that the surrounding stroma was coming under attack by macrophages, almost dissolving.”
The findings are preliminary, and further work is needed to better understand how the therapy works and how it can be best combined with other therapies, Dr. Vonderheide explained. The Abramson research team is launching another phase I trial to test the antibody in patients with metastatic melanoma, in combination with another experimental agent that stimulates T cells to attack tumor cells.
NCI Cancer Bulletin for April 5, 2011 - National Cancer Institute
No hay comentarios:
Publicar un comentario