Scientists at the Barbara Ann Karmanos Cancer Institute in Detroit received nearly $3 million to study an immunotherapy for triple-negative breast cancer. The five-year NIH research project (RO1) grant supplements a $2 million, four-year NIH RO1 grant to Karmanos that funds a treatment protocol for women with Her2-negative metastatic breast cancer using targeted T-cell immunotherapy.
Lawrence G. Lum, M.D., professor of medicine and immunology and microbiology at Karmanos and Wayne State University School of Medicine, and his research team are conducting a Phase II trial in women with stage II and III Her2/neu and triple-negative breast cancer. A total of 40 patients will be accrued for this study.
The candidate, an anti-CD3 x anti-Her2/neu bispecific antibody (Her2Bi)-armed activated T-cell immunotherapy, will be given in combination with neoadjuvant chemotherapy. The research group believes this treatment combination will increase the elimination of disease at the time of surgery. The targeted T cells not only kill cancerous cells but also enhance the body's ability to detect those cancerous cells. This could lead to long-term, anticancer immunity to prevent the recurrence of disease, according to the scientists.
The Karmanos Cancer Institute is reportedly the only cancer center in the U.S. offering bispecific antibody-targeted T-cell immunotherapies. Dr. Lum is the inventor of these bispecific antibody-armed T cells.
Cancer cells with low hormone receptor status, or none at all, are very difficult to treat since they have few or no receptors that are responsive to traditional chemotherapy antibodies. Less than 25% of all patients with triple-negative breast cancer respond well to chemotherapy and surgery, according to the researchers, and many suffer from a poor prognosis following treatment. The relapse rate is reportedly 80%.
“We're targeting a group that no one else can treat,” Dr. Lum notes. “We're trying to increase the complete pathological remission rate. Only about 20 percent of the women are Her2 positive. That leaves about 80 percent of the women who can't get antibody therapy such as Herceptin.”
The first step in the process of arming T cells is extracting the cells through apheresis. The cells are then cultivated and expanded in the lab and armed with the bispecific antibody, which programs the T cells to attack the tumors. Next, the armed T cells are frozen and preserved until they are ready to be infused into the patient after chemotherapy. A biopsy is performed following chemotherapy to see how much of the tumor was eliminated.
The research team checks the type and function of the lymphocytes in the tumor biopsy and determines the number of cancer tumor stem cells that are present. Patients will then receive four infusions of T cells, followed by surgery to remove the remaining tumor. At the time of surgery, the lymphocytes are tested for their function, and the number of remaining cancer stem cells is evaluated.
In the Phase I trial involving 19 women with all types of metastatic disease, Dr. Lum showed that infusions of Her2Bi-armed T cells are safe for the patient, induce immune responses that kill breast cancer cells, stabilize the disease, and promote a promising, partial clinical response. The results also indicate that targeted T-cell infusions work to vaccinate patients against their own tumors.
“We're hoping that when you eliminate the remaining tumor through immunotherapy and vaccinate the patient against the tumor, we would then see an increased number of women who were cured at that point in time,” Dr. Lum says.