Researchers transfer immune response to myeloma patient

Nov 27 2007

Researchers at the University of Arkansas for Medical Sciences (UAMS) have for the first time transferred an immune response in a healthy individual to a patient with multiple myeloma, a cancer of the bone marrow, showing promise for cancer vaccination.

In the study, conducted in the UAMS Myeloma Institute for Research and Therapy, a healthy individual was immunized with a cancer protein that can kick start the body's immune system to kill cancer cells. The cancer-killing antibodies produced by the healthy patient's immune system were then transferred via stem cell transplant to her twin sister, who had been diagnosed with multiple myeloma, in conjunction with chemotherapy.

The same immune response was subsequently observed in the patient, who remains in remission nearly three years after the transplant. An article on the study, “Immunization with a recombinant MAGE-A3 protein after high-dose therapy for myeloma” was published in the November/December 2007 issue of the Journal of Immunotherapy .

“Vaccination therapies have not yet been proven clinically effective for myeloma, possibly due to disruptions in the patient's immune system caused by chemotherapy or the disease itself,” said Frits van Rhee, M.D., Ph.D., leader of the research team and director of clinical research in the Myeloma Institute. “The ability to define and transfer an immune reaction from a healthy donor to a patient with multiple myeloma may give us another tool with long-lasting protection against disease recurrence.”

Van Rhee, also a professor in the UAMS College of Medicine, said that the donor and patient being identical twins provided an ideal situation to test the vaccination. Because the stem cells came from an identical twin, the researchers were able to avoid immunosuppressive therapy that would normally be necessary and could have hampered the immune response, he said.

The vaccine targeted a “cancer-testis” antigen known as MAGE-A3. Cancer-testis antigens are a group of proteins which have been found to be produced in cancerous cells but not in normal tissues. Cancer testis antigen-targeted therapy will therefore only destroy the malignant tissues which express them, making this type of therapy far less toxic than non-specific chemotherapies, van Rhee said.

After receiving the stem cell transplant, the patient also was vaccinated to boost the anti-myeloma response. The vaccines produced strong antibody and cellular responses in both the donor and the patient, said the researchers.

The MAGE-A3 vaccine used in this study is manufactured by Glaxo-Smith-Kline, and is currently showing promise in Phase III trials in small cell lung cancer, the researchers said.

They said the next step in the research is a larger-scale vaccination trial of myeloma patients, van Rhee said.

Lead author of the research article was Susann Szmania, a research assistant in the UAMS Myeloma Institute for Research and Therapy. Other authors from the Myeloma Institute were Guido Tricot, M.D., Ph.D.; Katie Stone, research assistant; Fenghuang Zhan, M.D., assistant professor in the UAMS College of Medicine; Amberly Moreno, research assistant; Brad Thuro, research assistant; John D. Shaughnessy Jr., Ph.D., chief of the basic sciences division; Bart Barlogie, M.D., Ph.D., director of the Myeloma Institute; and van Rhee.

Joining the UAMS researchers in the study was Sacha Gnjatic and Lloyd J. Old of the Ludwig Institute for Cancer Research in New York, N.Y.; Jos Melenhorst and John Barrett of the Stem Cell Allogenic Transplantation Section in the National Heart, Lung, and Blood Institute of the National Institutes of Health; and Vincent G. Brichard of GlaxoSmithKline Biologicals in Rixensart, Belgium.

The Myeloma Institute, a part of the UAMS Winthrop P. Rockefeller Cancer Institute, has performed more blood stem cell transplants for myeloma than any other facility in the world. UAMS treats more than 2,250 patients with myeloma annually at the Myeloma Institute – more myeloma patients than are treated at any other facility in the country.

UAMS is the state's only comprehensive academic health center, with five colleges, a graduate school, a medical center, six centers of excellence and a statewide network of regional centers. UAMS has 2,538 students and 733 medical residents. Its centers of excellence include the Winthrop P. Rockefeller Cancer Institute, the Jackson T. Stephens Spine & Neurosciences Institute, the Myeloma Institute for Research and Therapy, the Harvey & Bernice Jones Eye Institute, the Psychiatric Research Institute and the Donald W. Reynolds Institute on Aging. It is one of the state's largest public employers with about 9,600 employees, including nearly 1,000 physicians who provide medical care to patients at UAMS, Arkansas Children's Hospital, the VA Medical Center and UAMS' Area Health Education Centers throughout the state. UAMS and its affiliates have an economic impact in Arkansas of $5 billion a year. For more information, visit http://www.uams.edu.

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