More than a decade ago, scientists at the National Cancer Institute began investigating the idea of using patients’ own immune cells to treat their HER2-positive cancers. The technique involved taking dendritic cells from their blood, then genetically modifying them to produce parts of the HER2 protein. The hope was that if the modified cells were then introduced back to the patient, they would generate an immune response against the cancer.
Now, the NCI team is reporting promising results from a small trial in patients whose tumors overexpress HER2. The trial, reported at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference in New York, involved 17 patients who received 5 injections of the vaccine at different strengths.
Among 11 patients who received the two highest doses—either 10 million dendritic cells or 20 million—six had a “clinical benefit,” according to a statement released at the conference. The vaccine was administered via skin injections. There were no side effects aside from minor reactions at the injection site, the investigators said.
"We are using a vaccine approach to generate an immune response to HER2, which is found at high levels on and drives the growth of several types of cancer, including breast, ovarian, lung, colorectal, and gastroesophageal cancers,” said Jay Berzofsky, M.D., Ph.D., chief of the vaccine branch at the NCI’s Center for Cancer Research, in the statement.
Berzofsky and his colleagues first described their vaccine in the American Association for Cancer Research (AACR) journal, Cancer Research, in 2008, when the field of immuno-oncology was in its infancy. In that paper, they reported that a similar vaccine eradicated large breast tumors and lung metastases in mice.
Dendritic cells are a subset of immune cells that have long been of interest to immuno-oncology researchers because they have the power to train T cells to attack cancer, even when it has spread beyond the original tumor site. Dendreon’s Provenge, approved to treat prostate cancer in 2010, is a personalized vaccine made from patients’ dendritic cells. It has struggled to catch on, but Dendreon—which was recently sold for the third time in three years—is trying a variety of tactics to expand the market for the product.
There are several other dendritic-cell approaches under investigation, including a gel developed by Dana-Farber and Harvard scientists that can be placed directly at tumor sites during surgery. The gel was formulated to activate dendritic cells. Earlier this year, the researchers reported that in mouse models of breast cancer, the gel eliminated metastases and prevented recurrences.
The NCI researchers who developed the dendritic-cell vaccine are planning to test the therapy in combination with drugs that inhibit immune checkpoints. Berzofsky said that he hopes the team will be able to investigate their theory that combining two immune-boosting therapies will increase the proportion of patients who can benefit from dendritic vaccines.