Building on the success of the HIV Vaccine Trials Network, the Hutchinson Center has launched a new trials network, the Cancer Immunotherapy Trials Network (CITN), centered at VIDD. The network, funded by the National Cancer Institute (NCI), is headed by Dr. Mac Cheever, member of the Clinical Research Division, and will share many of the resources developed by the HVTN to coordinate a national network of clinical trials. The CITN aims to test the top potentially promising immunotherapy drugs that could boost immune cells in fighting cancer.
“There is no question that the immune system plays a role in the outcome of cancer,” Cheever said.
Many currently available cancer treatments target cancer cells directly, but researchers believe that better cures for cancer could come from training our own immune cells to recognize tumor cells as targets to be destroyed. Stem cell transplants in the form of blood or bone marrow transplants, a treatment originally developed at the Hutchinson Center, are a means of curing leukemia using a donor’s immune cells to fight the patient’s cancer cells. Now researchers have to figure out how best to harness that power in their own immune systems to treat other types of cancer.
Like the development of a successful HIV vaccine, the testing of new immunotherapy drugs for clinical use in cancer treatment involves several hurdles to clear. A network of top immunotherapists to design and implement clinical trials for testing these potential drugs will be better suited to tackle the problem than individual scientists running single trials alone, said Dr. Vaishali Rajeev, administrative director of the CITN.
There are many existing agents for activating and augmenting immune responses. One of the main difficulties in developing cancer immunotherapy agents is that the drugs are not likely to do much on their own, but will need to be used in combinations of two or more, said Cheever. The reason for this is that T cells, the immune cells that have the potential to specifically attack cancer cells, need to be selectively activated, expanded in number and stimulated to survive long-term. It is unlikely that a single compound could accomplish all of these steps, especially as the treatments will also need to override the natural checks and balances our bodies have in place to prevent overexpansion of T cells.
For example, the former biopharmaceutical company Immunex developed a drug called Flt3 ligand that is a growth factor for dendritic cells, a type of immune cells that presents pieces of foreign proteins to T cells and B cells, training those cells to recognize foreign bodies. Flt3 ligand has been shown to cause a large increase in the number of dendritic cells in cancer patients, but by itself has no influence on tumor progression. Immunologists believe that this increased base of dendritic cells could provide a platform for a cancer vaccine, a manufactured antigen that would allow more of the body’s immune cells to recognize and fight tumors.
The CITN will start by testing agents from a list of the “top 20 immunotherapy agents” prioritized by the National Cancer Institute in cancer patients, Cheever said. Cheever worked extensively with the NCI over the past few years to develop this priority list, based on recommendations submitted by scientists in the field. The NCI aims to obtain or manufacture these agents, and support testing them through the CITN. The Hutchinson Center won the CITN funding in part because of Cheever’s work on this list, and also because the network could graft onto the successful structure of the HVTN.
“[HVTN Executive Director] Jim Kublin and his staff have been a great resource for advice on building a clinical trial network,” Rajeev said. Besides advice on how to best structure a trials network, the CITN will share space and management personnel with the HVTN, Rajeev said.
Additionally, UW Professor and Clinical Research Division member Dr. Nora Disis, a co-investigator on the CITN, has developed techniques to monitor T cells’ specific immune responses. These methods will be essential to assess how well the candidate drugs work in patients. The CITN trials will first assess whether the drugs expand the number and function of T cells that respond to cancer, and then will test whether they provide actual benefit to cancer patients.
The funding was awarded to the Hutchinson Center in September 2010, to start building the framework of the network, and the NCI is now reviewing applications from other leading U.S. institutions to become one of the network’s 25 member sites. Each of these applying institutions has submitted 3 concept ideas. The complete selection process of the CITN member sites will be completed in March. Although nothing is yet set in stone, the first trials will most likely focus on IL-15, a growth factor for activated T cells that has not yet been tested in cancer patients, Cheever said.