cule to tumor sites for an even stronger response.
“This immunotherapy has the potential to be used alone or in combination with conventional cancer treatments to develop and establish immune protection against cancer and its metastases,” says Wang.
Tapping into T cells to combat breast cancer
Masoud Manjili, D.V.M., Ph.D., member of the Cancer Cell Signaling program at Massey, is also at the forefront of groundbreaking research on cancer immunotherapy by targeting and manipulating specific parts of cancer cells.
Manjili and his team focused on overcoming two major barriers of cancer immunotherapy: tumor-induced T cell suppression and T cell-induced tumor editing and relapse. The T cells are a family of immune system cells that keep people healthy by identifying and launching attacks against threats such as bacteria, viruses or cancer. Anti-tumor T cells can both stop or slow down tumor growth on the one hand, but also cause changes in the tumor cells that could lead to tumor relapse on the other hand. “The ultimate goal of immunotherapy is to overcome tumor-induced immune suppression and at the same time induce tumor rejection without facilitating tumor escape and relapse,” says Manjili.
Through lab studies led by Manjili, Massey researchers effectively reprogrammed cells of the innate and adaptive immune systems to overcome a key cancer defense mechanism and develop long-lasting memory to reject breast cancer cells, guarding against tumor relapse. In a study published in the Journal of Immunology, the researchers discovered a way to improve Adoptive Cellular Therapy (ACT), a treatment for breast cancer that taps into the immune system, by activating certain cells which enhance T cells capability to fight blood-forming cells.
These findings could lead to clinical trials that test whether using immunotherapy in a neoadjuvant (prior to surgery) or adjuvant (after surgery) setting in breast cancer patients with a high risk of relapse could prime the patient’s immune system, much like a vaccine, to prevent the likelihood of relapse.
Unlocking new treatments for blood cancers
Translating Manjili’s research into clinical application is Amir Toor, M.D., hematologist-oncologist in the Bone Marrow Transplant Program and research member of the Developmental Therapeutics program at Massey. Toor’s research concentrates on training the immune system to prevent cancer cells from evading detection and destruction. Focusing on T cells and the important role they play in warding off cancer cells, Toor and his team of investigators launched a two-pronged approach.
The first step was directed at developing safe and non-toxic treatments to perform allogeneic (donor) stem cell transplantation. The second step involved understanding the donor immune system's response to cancer in donor stem cell transplantation to develop a way to train the patient's immune system to attack the cancer cells, ultimately allowing the patient to benefit from the immunotherapeutic effect without the accompanying risk.
The clinical trials developing these ideas have focused on utilizing either the donor's or the patient's own T cells to kill cancer cells. Toor says that the process works much like locks and keys. “The small antigens on the surface of foreign cells are keys and each T cell has a receptor or a lock,” he says. “If the antigen on the threatening cell fits in the T cell receptor, then the lock is released and the T cell’s deadly arsenal is unleashed on the threat. For the recipients, the keys are proteins unique to the patient and are absent in the donor, thus becoming targets for the donor T cells.”
Another Phase II clinical trial led by Toor is showing promise in providing lasting protection against the progression of multiple myeloma following an autologous (self) stem cell transplant. Exemplifying the lock and key analogy, a combination of two drugs is trying to make cancer cells easier targets. The first drug, azacitidine, forces the cancer cells to express proteins – the keys – which the patient’s T cells – the locks – recognize as foreign. The 