Researchers have seen promising results using a multipart treatment that manipulates tumors to turn into cancer vaccine factories, sending out signals to train the immune system to better attack cancer throughout the body.
Publishing their findings in Nature Medicine, Joshua Brody, MD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai in New York City,and colleagues conducted a Phase I/II open-label trial in which they injected a series of immune stimulants into the tumor sites of 11 people with indolent B-cell non–Hodgkin lymphoma.
One stimulant, Flt3L, recruits dendritic immune cells, which marshal other immune cells into action. Local radiation therapy causes tumors to display more antigens, which are signals that immune cells can recognize. The next stimulant, a TLR3 agonist, activates the dendritic cells, which in turn instruct CD8 T cells to kill malignant cells while sparing nonmalignant cells. Overall, this multipart therapy trains an army of immune cells to identify tumor cells and destroy them throughout the body.
“The in situ vaccine approach has broad implications for multiple types of cancer,” Brody said in a press release. “This method could also increase the success of other immunotherapies such as checkpoint blockade.”
In situ, means “in the original place” in Latin. In other words, the treatment focuses on the original site of cancer.
One person developed complete remission of cancer both at the site targeted by the treatment as well as at other sites in the body, a phenomenon known as an abscopal effect. Two other people experienced partial responses. Six of the participants saw their disease stabilize. Two people’s disease progressed after treatment.
Laboratory tests in mice showed that the vaccine considerably increased the effectiveness of checkpoint inhibitors, immunotherapy drugs that promote T-cell activity, when the therapies were used in combination.
Scientists recently launched a clinical trial of the vaccine in combination with the PD-1 checkpoint inhibitor Keytruda (pembrolizumab) as a treatment for lymphoma, breast cancer and head and neck cancer. Laboratory testing in mice is also under way to evaluate the combination regimen as a treatment for liver and ovarian cancer.
To read the study abstract, click here.
To read a press release about the study, click here.