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A potent
anti-tumor gene introduced into mice with metastatic melanoma
has resulted in permanent immune reconfiguration and produced
a complete remission of their cancer.
The
research funded by a National Institutes of Health grant
has paved the way for a new clinical trial in humans funded
by the V Foundation for Cancer Research.
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Nov.
18, 2010
INDIANAPOLIS
-- A potent anti-tumor gene introduced into mice with metastatic
melanoma has resulted in permanent immune reconfiguration and
produced a complete remission of their cancer, according to an
article to be published in the December 2010 issue of the Journal
of Clinical Investigation. The online version is now available.
Indiana
University School of Medicine researchers used a modified lentivirus
to introduce a potent anti-melanoma T cell receptor gene into
the hematopoietic stem cells of mice. Hematopoietic stem cells
are the bone marrow cells that produce all blood and immune
system cells.
The T cell
gene, which recognizes a specific protein found on the surface
of melanoma, was isolated and cloned from a patient with melanoma.
The gene-modified stems cells were then transplanted back into
hosts and found to eradicate metastatic melanoma for the lifetime
of the mice.
"We found
that the transplantation of gene-modified hematopoietic stem cells
results in a new host immune system and the complete elimination
of tumor," reported Christopher E. Touloukian, M.D., an assistant
professor of surgery and immunology at the IU School of Medicine
and a member of the Indiana University Melvin and Bren Simon Cancer
Center. "To date, cancer immunotherapies have been hampered by
limited and diminishing immune responses over time. We believe
this type of translational model opens new doors for patients
with melanoma and potentially other cancers by taking advantage
of the potent regenerative capacity of hematopoietic stem cells
and new advances in gene therapy."
This research
was funded by a National Institutes of Health grant.
It has paved
the way for a new clinical trial in humans funded by the V Foundation
for Cancer Research. The pilot phase I trial will involve treatment
of 12 patients and focus primarily on the safety and efficacy
of the therapy, said Touloukian, who is the senior author on the
JCI paper and the principal investigator for the clinical
study. The clinical trial is expected to begin accruing patients
by late 2011.
In 2010, more
than 68,000 patients will be diagnosed with melanoma and the disease
will be associated with approximately 9,000 deaths. The state
of Indiana has the 11th highest rate of melanoma incidence of
all 50 states. Current treatments for metastatic melanoma, though
exciting and innovative, have been highly toxic and largely unsuccessful
with the most patients dying within 6 to 12 months after diagnosis.
Media Contacts
Mary Hardin
IU School of Medicine
mhardin@iupui.edu
317-274-7722
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