Made in City of Hope: T cells – enlisting the immune system to beat cancer

November 20, 2014 | by City of Hope

The body’s immune system is usually adept at attacking outside invaders such as bacteria and viruses. But because cancer originates from the body’s own cells, the immune system can fail to see it as foreign. As a result, the body’s most powerful ally can remain largely idle against cancer as the disease progresses. Immunotherapy in general seeks to spur the immune system to action, helping the body fight cancer. One type of immunotherapy —T cell therapy — reprograms immune cells known as T cells to recognize and destroy cancer cells.

Stephen Forman Stephen J. Forman, the head of City of Hope’s bone marrow transplant program, is leading a wave of T cell clinical trials, all of which are moving the treatment out of the lab and directly to patients.

A wave of clinical trials

Normally, T cells attack bacteria and other infectious agents. In T cell therapy, T cells are isolated from a sample of the patient’s blood, then genetically engineered to seek out and attack a specific cancer. Researchers grow millions of these engineered T cells in the laboratory. The engineered cells are reinfused into the patient, where they go to work eliminating cancer.

Stephen J. Forman, M.D., the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation, has long pursued breakthrough treatments for hematologic cancers and blood-related disorders, and heads up City of Hope’s bone marrow transplant program. Under his direction, a wave of T cell clinical trials is underway, all of which are moving the treatment out of the lab and directly to patients.

A series of firsts

City of Hope was among the first institutions to conduct in-human T cell therapy trials for patients with lymphoma, neuroblastoma (a childhood cancer) and glioma (a type of brain tumor). In 2013, Forman’s team was the first to use altered T cells to treat patients with malignant lymphoma as part of the stem cell transplant regimen. Forman’s team is now expanding this therapeutic platform to treat patients with both lymphoma and leukemia who are not undergoing a stem cell transplant. Later this year, City of Hope will open a first-in-human clinical trial evaluating a new T cell product for the treatment of glioma brain tumors, and will be the first in the world to treat patients with acute myelogenous leukemia (AML) using T cell therapy.

It could only be made here

Researchers in the T Cell Therapeutics Research Laboratory (TCTRL), led by Christine Brown, Ph.D., Xiuli Wang, M.D., Ph.D. and Saul Priceman, Ph.D., conduct basic science experiments to reprogram a patient’s T cells to recognize and destroy their cancer most effectively, then apply them when designing first-in-human clinical trials.

Administration of the altered T cells is subject to oversight from the Food and Drug Administration, as well as other regulatory agencies. City of Hope has a team dedicated to T cell initiatives. It ensures that these therapies are moved forward as quickly and safely as possible within regulatory guidelines, allowing clinicians and researchers to focus on the T cells.

At The Miller Family Translational Technologies Center at City of Hope, dedicated TCTRL staff engineer and grow a patient’s T cells.

City of Hope’s Division of Transfusion Medicine supports these trials in two ways. T cells are collected from patients at the Donor Apheresis Center. Using processes developed through years of experience in stem cell transplantation, the Stem Cell Processing Laboratory prepares the engineered T cells for reinfusion into the patient.

Collaborating with the TCTRL, City of Hope’s Clinical Immunobiology Correlative Studies Laboratory evaluates samples and specimens obtained from patients in trials, giving the T cell therapy team a clear picture of the engineered T cells and the potential impact on the individual’s tumor, body and immune system. City of Hope makes possible the full circle of translational medicine.

Moving forward

T cell therapy research at City of Hope is extending beyond the important work on blood and bone marrow cancers, and brain tumors. Scientists and doctors are now investigating T cell therapy’s potential against multiple myeloma, ovarian, breast and prostate cancers, with clinical trials expected to open in two to three years. These are some of the deadliest forms of cancer that currently lack powerful, lifesaving treatments. With these trials, that could change.

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Read more articles from City of Hope's annual report.

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