Currently, most cancer treatments involve chemotherapy and radiation. Both of these therapies target rapidly-replicating cells in the body, and result in the death of these cells. Cancer cells are targeted by these therapies; unfortunately, many healthy cells are also targeted. This results in side effects ranging from nausea, to hair loss, skin problems, anemia, and a compromised immune system. In addition, the current therapies are may have low efficacy rates in certain types of cancers or late stage cancers, and even after a patient enters remission, he or she may eventually relapse.
One new therapy recently put through clinical trials actually helps train a patient’s immune system to fight ovarian cancer tumors. The vaccine therapy uses tumor cells from the patient to train immune cells from the patient to fight the cancer, thus creating a personalized vaccine for each individual patient. The process involved removing tumor cells and a type of white blood cell from patients. The white blood cells, called monocytes, are innate immune cells. The monocytes will mature into cells called Dendritic Cells, which will help to prime the adaptive immune system by ingesting foreign invaders and altered host cells (called altered self). After the Dendritic Cell ingests a problematic cell, it presents antigen to the adaptive immune system. This activates adaptive immune cells, called T cells. The T cells are able to specifically recognize the problematic cell (either foreign or altered self) and will work to remove other infectious or cancerous cells.
The clinical trial involved the use of Dendritic Cell therapy. The procedure involved isolating monocytes from the patient’s blood. Once monocytes have been isolated from the patient’s blood, they are matured into Dendritic cells, and are expanded in a cell culture system. This increases the number of Dendritic Cells available to function in the patient’s immune system. After the Dendritic Cells have been expanded, they are incubated with tumor cells. The Dendritic Cells will ingest the tumor cells, and display the tumor antigen on the cell surface. The Dendritic Cells are next injected back into the patient, where they will activate T cells to fight the ovarian cancer tumor. This is a typical procedure used in Dendritic Cell therapy.
For the clinical trial studying ovarian cancer treatment, 25 of 31 patients who developed anti-tumor responses but still were affected by disease, were additionally treated with adoptive T cell therapy. T cells from the patient were expanded and primed in cell culture, then injected back into the patient, similar to the Dendritic Cell therapy. The T cells, which are the adaptive part of the immune system, are able to recognize and kill ovarian cancer cells in the patient. The T adoptive T cell therapy was supplemented with a cancer drug called Avastin, which helps prevent growth of blood vessels to feed the tumor.
A major advantage to using Dendritic Cell therapy and adoptive T cell transfer is that both of these therapies are personalized to the patient. All cells used in the therapy, including the cancer cells that prime the immune cells, originate from the patient. This means that the Dendritic Cells and T cells will be specifically designed to fight the patient’s own cancer, as opposed to cancer cells obtained from other sources. In addition, this prevents any potential adverse immune reaction that can occur when patients receive transplants from other donors, such as bone marrow or stem cell transfers.
This early clinical trial studied 35 patients with stage 3 and stage 4 ovarian cancer. Of the patients treated with only the Dendritic Cell vaccination, 61% had a noticeable clinical response. Of the patients treated with both the Dendritic Cell vaccination and the adoptive T cell transfer, 75% showed a clinical benefit. Eight patients had no signs of disease at the end of the study, and continued to receive maintenance vaccinations to prevent relapse of the cancer. One of the 31 patients even went into complete remission, meaning the cancer was completely undetectable even 42 months after the end of the study. This was the first such clinical study in which two immunotherapies were combined to treat cancer. The results provide exciting evidence that by combining two powerful anti-cancer therapies, patients’ immune systems can have a better chance to fight cancer.