The field of cancer immunotherapy received an important boost last week with the FDA’s approval of the first therapeutic cancer vaccine, sipuleucel-T (Provenge). The vaccine was approved for use in some men with metastatic prostate cancer based on the results of a phase III randomized trial called IMPACT that demonstrated a more than 4-month median improvement in overall survival compared with a placebo vaccine. However, because of the way in which the vaccine is produced, its availability will be very limited for at least the next 12 months.
They continue:
The approval validates the concept of an active treatment approach such as immunotherapy, which is intended to train the immune system to attack cancer cells and potentially get a response “that can last for months or even years down the road,” said Dr. James Gulley of NCI’s Center for Cancer Research, who has led several clinical trials of a different therapeutic vaccine for prostate cancer. (See the sidebar.)
Despite the approval and several decades of research, Dr. Gulley acknowledged that immunotherapy is still an emerging field. “We’re just now learning how to develop potent-enough vaccines, what patient populations they are most appropriate for, and how to augment them by adding other therapies,” he said.
The patient specific part is characterized as follows:
Unlike some other therapeutic cancer vaccines under development, sipuleucel-T is customized to each patient. In the days prior to treatment, patients undergo a procedure called leukapheresis to isolate antigen-presenting cells (APCs) from their blood. These APCs include dendritic cells and macrophages, among other cells, that can “present” markers, or antigens, on their surfaces that are recognized by other immune cells, thereby sparking an immune response.
The APCs are sent to a Dendreon facility where they are cultured with a proprietary manufactured protein. The end result is a vaccine with hundreds of millions of “activated” APCs loaded with an antigen commonly found on most prostate cancer cells, called prostatic acid phosphatase (PAP). The vaccine is returned to the patient’s treating physician and infused into the patient, with the intent of spurring powerful immune system cells, T cells, to neutralize tumor cells that express PAP. Patients receive three treatments over the course of 4 to 6 weeks, with each round requiring the same manufacturing process.
This path to cancer treatment is one of the ways to have the body attack the unwelcome cells. This has been a path used for decades by Rosenberg at NCI on melanoma with limited results.
In another posting at NCI they recount a somewhat negative finding where even with what were considered localized prostate cancers, those which were assumed to be in the prostate and not spread, cancer cells were discovered in the blood stream. NCI states:
Researchers from Massachusetts General Hospital (MGH) have isolated tumor cells circulating in the blood of patients with localized prostate cancer as well as from patients with advanced disease. The researchers were then able to characterize genetic changes in these circulating tumor cells (CTCs), which they stressed was an important step toward potentially using CTCs to guide the selection of therapies and improve patient care. The findings appeared in the March 31 Science Translational Medicine.
The discovery of CTCs in men with localized disease was unexpected, but this may simply have been because until now the technology had not been sensitive enough to capture the cells in patients with early-stage disease, noted one of the lead authors, Dr. Sunitha Nagrath of MGH and Harvard Medical School.
Clearly this is one step forward and a step sideways.
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