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Cancer Immunotherapy
Research teams in the Center for Cancer and Immunology Research at Children’s National study what is known as cancer immunotherapy, or teaching the body’s immune system to more effectively combat cancer. Studies include development of cancer vaccines, which could additionally be applied as therapies to enhance the body’s positive response to standard treatment protocols and lessen the side effects of the current standards of care. Researchers hope that they can lessen the side effects of conventional treatments, increase the likelihood of the success of those treatments, and one day find a new way, effective way to treat childhood cancers without the use of protocols that carry with them such harsh after effects.
Cancer vaccines
Children’s Chief of the Division of General and Thoracic Surgery, Anthony Sandler, MD, is developing a vaccine and delivery system applies a tumor’s specific genetic material to induce, or teach, the body’s own immune system to respond and prevent tumor growth or re-growth. Treatments are tailored to an individual tumor’s proteins-allowing for a personalized molecular medicine approach to care. A novel delivery system involves the creation of synthetic microparticles known as “immune stimulatory antigen loaded particles” (ISAPs), that consist of specific tumor antigens as well as immune stimulatory agents. The ISAPs are detected and engulfed by specialized immune cells and sensed to be immune-stimulating “foreign bodies.” ISAPs have been shown to be effective at blocking the growth of tumors in mice by inducing activation of immune cells that then stimulate the immune system to specifically target the tumor whose antigens match those that are loaded in the particles – creating tumor specific immunity. The research team is currently exploring the role of regulatory T-cells in inhibiting the ISAP impact on tumor growth. If successful, this vaccine could be used for tumors like neuroblastoma as a follow-up to standard therapies that include chemotherapy and surgical resection to drastically reduce the likelihood of recurrence.
Immunotherapy and bone and marrow transplantation
Children's Chief of the Division of Blood and Marrow Transplantation, Terry Fry, MD, studies a similar vaccine approach to boost the effectiveness of bone and marrow transplantation either during or following transplant. Specific tumor antigens are introduced to donor t-lymphocytes in order to prepare those t-lymphocytes to effectively target the tumor’s cells once introduced into the body. T-lymphocytes are the immune cells that fight infection and have been shown to effectively kill tumors if able to target the tumor cells alone. The targeted t-lymphocytes can then be infused to prevent or halt a relapse of leukemia. Currently, such adoptive therapy, or infusion of donor t-lymphocytes, is a standard treatment to slow or halt relapse of leukemia, but without specifically targeting tumor cells, the donor t-lymphocytes have a high likelihood of attacking normal organs as well, which creates serious side effects for the patient. Targeting the cells will reduce the side effects of this treatment while effectively halting relapse at the same time.
Additionally, Dr. Fry and his team study whether these donor t-lymphocytes could be infused into the body of a patient at the time of bone and marrow transplantation (BMT) to bind to tumor cells, then kill these cells and limit or stop tumor growth as part of the initial therapy and as part of preventive treatment moving forward, rather than after the fact to prevent relapse.
Adoptive T cell therapy of tumors
Stanislav Vukmanovic, MD, PhD, studies adoptive T cell therapy for cancer using a combination of alloreactivity (the immune system reactivity responsible for transplant rejection) and high avidity T cells. This approach can bypass a partial tolerance of the body’s immune system for tumor antigens and outgrowth of tumor variants with loss of tumor antigen or HLA expression, both of which dramatically reduce the ability of the immune system to recognize and attack tumors. Dr. Vukmanovic's laboratory has created a transgenic mouse, called MTB, with increased TCR avidity in a diverse T cell population. Strong alloreactive responses of transgenic T cells against targets with low antigen expression can be used as an effective adoptive transfer of tumor immunity in vivo. Alloreactive MTB T cells could be an effective therapeutic approach counteracting tumor evasion of the immune system and a source of high avidity T cells with multiple specificities.
Faculty who study cancer immunotherapy:
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