City of Hope Receives $5 Million Grant to Develop T Cell Treatment Targeting Brain Tumor Stem Cells

DUARTE, Calif.--(BUSINESS WIRE)--

City of Hope was granted a $5,217,004 early translational research award by the California Institute for Regenerative Medicine (CIRM) to support the development of a T cell-based immunotherapy that re-directs a patients own immune response against glioma stem cells. City of Hope has been awarded more than $49.7 million in grant support from CIRM since awards were first announced in 2006.

City of Hope is a pioneer in T cell immunotherapy research, helping to develop genetically modified T cells as a treatment for cancer. This strategy, termed adoptive T cell therapy, focuses on redirecting a patients immune system to specifically target tumor cells, and has the potential to become a promising new approach for treatment of cancer.

In this research, we are genetically engineering a central memory T cell that targets proteins expressed by glioma stem cells, said Stephen J. Forman, M.D., Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and director of the T Cell Immunotherapy Research Laboratory. Central memory T cells have the potential to establish a persistent, lifelong immunity to help prevent brain tumors from recurring.

The American Cancer Society estimates that more than 22,000 people in the U.S. will be diagnosed with a brain tumor this year, and 13,700 will die from the disease. Glioma is a type of brain tumor that is often difficult to treat and is prone to recurrence. Currently, less than 20 percent of patients with malignant gliomas are living five years after their diagnosis. This poor prognosis is largely due to the persistence of tumor-initiating cancer stem cells, a population of malignant cells similar to normal stem cells in that they are able to reproduce themselves indefinitely. These glioma stem cells are highly resistant to chemotherapy and radiation treatments, making them capable of re-establishing new tumors.

Researchers at City of Hope previously have identified several proteins as potential prime targets for the development of cancer immunotherapies, such as interleukin 13 receptor alpha 2, a receptor found on the surface of glioma cells, and CD19, a protein that is active in lymphoma and leukemia cells. Both investigational therapies are currently in phase I clinical trials. Forman is the principal investigator for the newly granted study which will develop a T cell that targets different proteins expressed by glioma stem cells. Christine Brown, Ph.D., associate research professor, serves as co-principal investigator, and Michael Barish, Ph.D., chair of the Department of Neurosciences, and Behnam Badie, M.D., director of the Brain Tumor Program, serve as co-investigators on the project.

Because cancer stem cells are heterogeneous, our proposed therapy will target multiple antigens to cast as wide a net as possible over this malignant stem cell population, said Brown.

While in this effort, we are targeting a neurological cancer, our approach will lead to future studies targeting other cancers, including those that metastasize to the brain, added Barish.

The CIRM grant will help us to build a targeted T cell therapy against glioma that can offer lasting protection, determine the best way to deliver the treatment, establish an efficient process to manufacture these T cells for treatment, and get approval for a human clinical trial, said Badie.

City of Hope is also a collaborative partner providing process development, stem cell-derived cell products and regulatory affairs support in two other CIRM-funded projects that received early translational research grants. Larry Couture, Ph.D., senior vice president of City of Hopes Sylvia R. & Isador A. Deutch Center for Applied Technology Development and director of the Center for Biomedicine & Genetics, is working with Stanford University and Childrens Hospital of Orange County Research Institute on their respective projects.

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City of Hope Receives $5 Million Grant to Develop T Cell Treatment Targeting Brain Tumor Stem Cells

Stem-cell-growing surface enables bone repair

ScienceDaily (May 23, 2012) University of Michigan researchers have proven that a special surface, free of biological contaminants, allows adult-derived stem cells to thrive and transform into multiple cell types. Their success brings stem cell therapies another step closer. To prove the cells' regenerative powers, bone cells grown on this surface were then transplanted into holes in the skulls of mice, producing four times as much new bone growth as in the mice without the extra bone cells.

An embryo's cells really can be anything they want to be when they grow up: organs, nerves, skin, bone, any type of human cell. Adult-derived "induced" stem cells can do this and better. Because the source cells can come from the patient, they are perfectly compatible for medical treatments.

In order to make them, Paul Krebsbach, a professor of biological and materials sciences in the School of Dentistry, said, "We turn back the clock, in a way. We're taking a specialized adult cell and genetically reprogramming it, so it behaves like a more primitive cell."

Specifically, they turn human skin cells into stem cells. Less than five years after the discovery of this method, researchers still don't know precisely how it works, but the process involves adding proteins that can turn genes on and off to the adult cells.

Before stem cells can be used to make repairs in the body, they must be grown and directed into becoming the desired cell type. Researchers typically use surfaces of animal cells and proteins for stem cell habitats, but these gels are expensive to make, and batches vary depending on the individual animal.

"You don't really know what's in there," said Joerg Lahann, an associate professor of chemical engineering and biomedical engineering. For example, he said that human cells are often grown over mouse cells, but they can go a little native, beginning to produce some mouse proteins that may invite an attack by a patient's immune system.

The polymer gel created by Lahann and his colleagues in 2010 avoids these problems because researchers are able to control all of the gel's ingredients and how they combine. "It's basically the ease of a plastic dish," said Lahann. "There is no biological contamination that could potentially influence your human stem cells."

Lahann and colleagues had shown that these surfaces could grow embryonic stem cells. Now, Lahann has teamed up with Krebsbach's team to show that the polymer surface can also support the growth of the more medically-promising induced stem cells, keeping them in their high-potential state. To prove that the cells could transform into different types, the team turned them into fat, cartilage, and bone cells.

They then tested whether these cells could help the body to make repairs. Specifically, they attempted to repair 5-millimeter holes in the skulls of mice. The weak immune systems of the mice didn't attack the human bone cells, allowing the cells to help fill in the hole.

After eight weeks, the mice that had received the bone cells had 4.2 times as much new bone, as well as the beginnings of marrow cavities. The team could prove that the extra bone growth came from the added cells because it was human bone.

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Stem-cell-growing surface enables bone repair

Stem cell treatment for heart failure takes small step forward

Researchers at the Technion-Israel Institute of Technology in Haifa, Israel, reported Tuesday that they had removed skin cells from two patents with heart failure, returned those cells to an embryonic state, and then transformed them into beating heart cells that could communicate with the patients existing heart tissue.

We have shown that it is possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young the equivalent to this stage of his heart cells when he was just born, study leader Dr. Lior Gepstein said in a statement.

The discovery marks a small step toward a long-sought goal: using stem cells to regrow the cardiac tissue that is damaged in heart attacks. (The Times reported on the quest in February, 2011.) But it doesnt mean that patients with heart failure are likely to get shiny new hearts through stem cell treatments anytime soon.

Several hurdles stand in the way of using induced pluripotent stem cells, as the skin-derived cells are called, to reverse heart attack damage. The Israeli researchers acknowledged several. Such cells are known to spin out of control and cause cancer. Stem cell-derived cardiac cells have also had problems coordinating with normal heart rhythms. The team will need to be able to generate larger numbers of the cells before it can test the treatment, and will need to perfect transplant methods.

And if all those hurdles are crossed, scientists still wont know if the technology will work in people. What we produce in an animal model or in a petri dish is hardly what happens in a human. This is a first step. It will take five, 10, 15, maybe 20 years to reach fruition at the soonest, said Dr. Shephal Doshi, director of electrophysiology and pacing at Saint Johns Health Center in Santa Monica.

Most patients will have to wait to take advantage of other types of stem cell cures for heart failure as well including treatments that use cells derived from bone marrow to stimulate heart regeneration, treatments that use cardiac stem cells removed from the heart to build heart tissue and insert it back into the diseased organ and treatments that attempt to stimulate cardiac stem cells in place in the heart into action to rebuild tissues. These technologies are in varying stages of testing and development.

The Centers for Disease Control and Prevention has more information about heart failure in the U.S.

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Stem cell treatment for heart failure takes small step forward