Patient's Own Infection-Fighting T Cells Put Late-Stage Melanoma Into Long-Term Remission

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Patient's Own Infection-Fighting T Cells Put Late-Stage Melanoma Into Long-Term Remission - Without Chemotherapy or Radiation
 Case is first to show safety and effectiveness of using cloned cells alone
                               to kill tumors

    SEATTLE, June 18 /PRNewswire/ -- Researchers describe the first
successful use of a human patient's cloned infection-fighting T cells as
the sole therapy to put an advanced solid-tumor cancer into long-term
remission. A team led by Cassian Yee, M.D., an associate member of the
Clinical Research Division at Fred Hutchinson Cancer Research Center,
reports these findings in the June 19 issue of the New England Journal of
Medicine.

    Yee and colleagues removed CD4+ T cells, a type of white blood cell,
from a 52-year-old man whose Stage 4 melanoma had spread to a groin lymph
node and to a lung. T cells specific to targeting the melanoma were then
expanded vastly in the laboratory using modifications to existing methods.
The lab-grown cells were then infused into the patient with no additional
pre- or post-conditioning therapies, such as growth-factor or cytokine
treatment. Two months later, PET and CT scans revealed no tumors. The
patient remained disease free two years later, when he was last checked.

    "We were surprised by the anti-tumor effect of these CD4 T cells and
its duration of response," Yee said. "For this patient we were successful,
but we would need to confirm the effectiveness of therapy in a larger
study."

    Yee cautioned that these results, presented in the journal's "Brief
Report" section, represent only one patient with a specific type of immune
system whose tumor cells expressed a specific antigen. More studies are
needed to confirm the effectiveness of the experimental T cell therapy. If
proven successful in more patients, Yee predicted this therapy could be
used for the 25 percent of all late-stage melanoma patients who have the
same immune-system type and tumor antigen.

    Using a patient's own immune system to combat cancer, called
immunotherapy, is a growing area of research that aims to develop
less-toxic cancer treatments than standard chemotherapy and radiation.

    The patient in the journal report was one of nine patients with
metastatic melanoma who were being treated in a recently completed clinical
trial to test dose-escalation of autologous CD4+ T cells. Earlier studies
performed by Yee used CD8+ T cells, which do not persist in the body
without the support of CD4+ T cells or growth factors such as interleukin
2. Yee and colleagues theorized that infusion of a massive dose of CD4+ T
cells would persist longer in the body because they make their own growth
factor, interleukin 2, while stimulating the anti-tumor effect of the
patient's existing CD8+ T cells. However, until recently there was no
feasible way to isolate and expand anti-tumor CD4+ T cells in the lab.

    The researchers were successful in all of these areas. The patient
received a dose of 5 billion cloned CD4+ T cells with specificity for the
melanoma-associated NY-ESO-1 antigen. The cells persisted for at least 80
days in the patient's body. And, even though only 50 percent to 75 percent
of the patient's tumor cells expressed the NY-ESO-1 antigen, the entire
tumor regressed following the infusion. The scientists postulated that the
patient's immune response was broadened to other antigens expressed by the
tumor cells. Follow-up tests showed T cell responses to two additional
tumor antigens, MAGE-3 and MART-1.

    Researchers in Yee's lab, the University of Washington School of
Medicine and the Ludwig Institute for Cancer Research in New York
collaborated on the research. The Burroughs-Wellcome Foundation, Damon
Runyon Cancer Research Foundation, Edson Foundation and National Cancer
Institute funded the study.

    At Fred Hutchinson Cancer Research Center, our interdisciplinary teams
of world-renowned scientists and humanitarians work together to prevent,
diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers,
including three Nobel laureates, bring a relentless pursuit and passion for
health, knowledge and hope to their work and to the world. For more
information, please visit http://fhcrc.org.



     CONTACT:
     Dean Forbes
     206-667-2896
     dforbes@fhcrc.org

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SOURCE Fred Hutchinson Cancer Research Center
http://www.fhcrc.org
CONTACT:
Dean Forbes, Media Relations of Fred
Hutchinson Cancer Research Center, +1-206-667-2896,
dforbes@fhcrc.org