A new therapy is offering hope to patients with a certain form of acute lymphoblastic leukemia (ALL). The drug recently received approval by the U.S. Food and Drug Administration, thanks in part to studies conducted by Anthony Stein, M.D., at City of Hope.
The drug Blincyto, also known by its generic name of blinatumomab, is a bispecific T-cell engager, or BiTE.
An emerging class of monoclonal antibody drugs, BiTE antibodies have a unique way to activate a patient’s immune system to attack cancer cells. One section of the antibody attaches to cancer cells while the other section activates the patient’s own disease-fighting T cells and redirects them to kill the cancer cells.
Stein, a clinical professor in the Department of Hematology and Hematopoietic Cell Transplantation, oversaw clinical trials of Blincyto at City of Hope for patients with a certain form of ALL that had returned after treatment and was resistant to therapy. “The approval of Blincyto represents a significant milestone in immunotherapy research,” he said. Clinicians now have a new therapy for patients diagnosed with a highly aggressive cancer for which there are limited treatment options.
Cancer cells are voracious eaters. Like a swarm of locusts, they devour every edible tidbit they can find. But unlike locusts, when the food is gone, cancer cells can’t just move on to the next horn o’ plenty. They have to survive until more food shows up — and they do.
Mei Kong, Ph.D., assistant professor in the Department of Cancer Biology, recently received $1.7 million from the National Cancer Institute to understand how cancerous cells survive their self-imposed famines.
Glutamine is an essential form of food for cancer cells. The amino acid provides the energy the cells need to survive and multiply. But malignant cells are gluttons and grow so rapidly they run through the glutamine stores, leaving themselves without their nutrition source. Although this should cause the cells to starve to death, it doesn’t.
Kong is working to uncover the tricks cancer cells use to stifle their hunger until the famine again turns to feast. So far she and her colleagues have found several proteins and molecular pathways involved in the process. The current grant will help them extend their studies, furthering our investment in scientific discovery to uncover possible new cancer therapies.
When it comes to research into the treatment of hematologic cancers, City of Hope scientists stand out. One study that they presented this week at the annual meeting of the American Society of Hematology suggests a new standard of care for HIV-associated lymphoma, another offers promise for the treatment of relapsing or treatment-resistant lymphoma, and still another points to more effective treatment for acute lymphoblastic leukemia.
Researchers from the Hematologic Malignancies and Stem Cell Transplantation Institute at City of Hope shared their findings at the annual ASH meeting, held Dec. 6 through 9, in San Francisco. More than 20,000 hematology professionals attended the annual conference, which highlights the hottest topics in the field.
Here are some of the highlights: » Continue Reading
Patients with HIV-associated lymphoma may soon have increased access to the current standard of care for some non-HIV infected patients – autologous stem cell transplants.
Impressive new data, presented Monday at the annual meeting of the American Society of Hematology (ASH) in San Francisco, indicate that HIV-associated lymphoma patients who meet standard eligibility criteria for transplants of their own stem cells respond well to the treatment, even in centers that do not have HIV-specific expertise. HIV infection has historically been viewed as reason to rule out autologous stem cell transplant – the standard of care for non-infected patients with relapsed or treatment-resistant lymphoma – due to their compromised immune system.
The new study could change that perception. It was led by Joseph Alvarnas, M.D., director of Medical Quality and Quality, Risk and Regulatory Management and a physician investigator at the Hematologic Malignancies and Stem Cell Transplantation Institute at City of Hope, and colleagues at Johns Hopkins Hospital. The study builds on previous research at City of Hope, including a crucial 2001 publication that was among the first internationally to show these transplants were possible for HIV patients. » Continue Reading
On its 10th birthday, the California Institute for Regenerative Medicine celebrated 10 stem cell therapies that have been approved for clinical trials, including an HIV/AIDS trial at City of Hope.
At the recent anniversary event at USC’s Broad Stem Cell Center, scientific leaders in the development of stem cell therapies for a range of diseases and conditions – such as AIDS, cancer, diabetes and blindness – reflected on the accomplishments of the last decade and thanked voters for their investment in research aimed at pushing the frontiers of medicine.
City of Hope has used its $55 million in CIRM funding to participate in every facet of stem cell research, including basic science, translational medicine, clinical trials and training the next generation of scientists in stem cell biology. John Zaia, M.D., the Aaron D. Miller and Edith Miller Chair in Gene Therapy and chair of the Department of Virology, said during his remarks at the event that CIRM also has encouraged academic institutions to partner with biotech companies to achieve results. » Continue Reading
When it comes to cancer, your family history may provide more questions than answers: How do my genes increase my risk for cancer? No one in my family has had cancer; does that mean I won’t get cancer? What cancers are common in certain populations and ethnicities?
City of Hope experts have some guidance. “Your genes are not your destiny, but they can play a role in the decisions you make related to cancer screenings, diet and interventions that you do along the way,” said Joseph Alvarnas, M.D., director of medical quality and an associate clinical professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope. “You can take an active role in how you move along in life, rather than be the passive recipient of the hand that genetics happens to deal to you.” » Continue Reading
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.
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. » Continue Reading
Hematologist Robert Chen, M.D., is boosting scientific discovery at City of Hope and, by extension, across the nation. Just ask the National Cancer Institute.
The institution recently awarded Chen the much-sought-after Clinical Investigator Team Leadership Award for boosting scientific discovery at City of Hope. He is one of just 11 researchers in the nation this year to receive the prestigious $100,000 grant from the NCI.
Fewer than 60 scientists have been granted the award since its inception five years ago.
The two-year NCI grant recognizes Chen’s exceptional merit as a clinical researcher whose innovative efforts are advancing therapies for lymphoma patients.
Chen, an assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation, specializes in Hodgkin lymphoma research and treatment. His recent leadership of clinical trials testing the drug brentuximab vedotin helped clear its use for treating certain Hodgkin lymphoma patients who don’t respond well to stem cell transplantation. » Continue Reading
Identifying cures for currently incurable diseases and providing patients with safe, fast and potentially lifesaving treatments is the focus of City of Hope’s new Alpha Clinic for Cell Therapy and Innovation (ACT-I).
The clinic is funded by an $8 million, five-year grant from the California Institute for Regenerative Medicine. The award is part of CIRM’s Alpha Stem Cell Clinics program, which aims to create one-stop centers for clinical trials focused on stem cell treatments for diseases.
Two trials were identified to launch the center, but additional trials are currently enrolling patients and will be part of this clinic. The first trials center on transplants of blood stem cells that have been modified to treat patients with AIDS and lymphoma, and on the use of neural stem cells – which naturally home to cancer cells – to deliver drugs directly to cancers hiding in the brain. Coming soon will be trials that use T cell immunotherapy, developed by researchers in City of Hope’s new Hematologic Malignancies and Stem Cell Transplantation Institute.
“We are committed to finding cures and treatments to diseases that are, for now, incurable,” said John Zaia, M.D., the Aaron D. Miller and Edith Miller Chair in Gene Therapy, chair of the Department of Virology and principal investigator for the stem cell clinic. “This grant recognizes City of Hope’s commitment to and leadership in this endeavor, as well as enables us to pursue the crucially important work of bringing the promising potential of stem cell treatments to fruition.” » Continue Reading
Chemotherapy drugs work by either killing cancer cells or by stopping them from multiplying, that is, dividing. Some of the more powerful drugs used to treat cancer do their job by interfering with the cancer cells’ DNA and RNA growth, preventing them from copying themselves and dividing.
Such drugs, however, like Hydroxyurea, do have drawbacks. One is that the body metabolizes them quickly. Patients need frequent doses to achieve the desired effects. Because the side effects of the drugs are already considerable, increased use of them raises the risk of negative reactions. Another drawback is that cancer cells develop rapid resistance to the drugs, reducing their effectiveness.
A team effort
As a physician, molecular pharmacologist Yun Yen, M.D., Ph.D., knows well the limitations of chemotherapy drugs. He partnered with medicinal chemist David Horne, Ph.D., to find — and improve — a molecule, or compound, to overcome these problems.
First, Yen selected a promising anti-cancer compound from the National Cancer Institute’s library of anti-cancer agents. Then, using data obtained with the help of the skilled laboratory scientists in City of Hope’s Core (or “Shared”) Services, Horne began to make structural adjustments to improve the molecule’s effectiveness. Core Services provides researchers, specialized expertise, testing and instrumentation in fields such as molecular modeling, screening, medicinal chemistry and cancer biology. Access to these services enabled Yen and Horne to determine, even before preclinical testing, how the compound worked. » Continue Reading