Neutrophil-Activating Therapy Eliminates Solid Tumors in Mouse Models and Induces Human Neutrophils to Kill Cancer Cells In Vitro

Treating laboratory mice with a novel neutrophil-activating therapy was associated with the elimination of several types of tumors and a reduction in the number and size of subsequent metastases, according to recent findings from Stanford Medicine. Edgar Engleman, MD, medical director of Stanford Blood Center, is the senior author of the research, which was published Jan. 26 in Cancer Cell. Postdoctoral scholar Ian Linde, PhD, is the study’s first author.

The study resulted from Linde injecting tumors in laboratory mice with various combinations of cytokines that Engleman’s laboratory had previously shown modulated the immune response to cancers. In initial studies, Linde injected a combination of tumor necrosis factor, a CD40 agonist and a tumor-binding antibody into the tumors of eight mice with melanoma. The therapy – called “neutrophil-activating therapy” by investigators – resulted in mobilization of large numbers of neutrophils in the blood that infiltrated and eliminated tumors in seven out of eight mice. They remained cancer free until the end of the study five months later.  Moreover, distant metastases in the lungs were also largely eliminated.

In a follow-up study of mice with cancers of the skin, lung, breast and colon, the therapy eliminated tumors in 7 of 10 mice with melanoma, 8 of 10 with mammary cancer, 8 of 10 with colon cancer and 4 of 10 with lung cancer. In contrast, no mice that were pre-treated with an antibody that eliminates neutrophils lived to the end of the experiment. According to researchers, these findings indicate that the cancer-killing activity was due to the tumor-infiltrating neutrophils.

Linde and his co-investigators also determined that the same combination therapy activates human neutrophils in vitro and enabled the lysis of human tumor cells. According to the investigators, the approach could be useful in treating people with many types of cancer.

“This suggests that we might be able to use activated neutrophils as a cell therapy,” Engleman said in a media statement. “We could remove a patient’s neutrophils and activate them in the laboratory before giving them back to the patient. This is completely different from current T cell-based cell therapies, and because there is no overlap, we might be able to use them in combination to great effect.”

Engleman and Linde have filed a patent application based on the research.