Download Treating Pediatric Leukemia Today

701 Grove Road  Greenville, SC 29605
Philanthropic Opportunity
Pediatric Leukemia Research Opportunity
Although our society enjoys great advances in medical technology, we still have much to learn.
Even today, many children with chronic, life-threatening illnesses are not promised cures. This
paper will review the current protocol of treatment for pediatric leukemia, examine other
innovative ways of treating cancer in general, suggest an alternative to the current treatment for
pediatric leukemia, and request your further involvement as a philanthropic partner.
At Greenville Hospital System, the Oncology Research Institute (ORI) and Children’s Hospital
have launched an initiative that seeks to produce a superior success rate for treatment of pediatric
leukemia that simultaneously alleviates much of its pain and side effects. In addition, ORI hopes
to conduct further research initiatives for children with other life-threatening, cancer-related
conditions.
Treating Pediatric Leukemia Today
Standard treatment for pediatric leukemia generally involves high-dose chemotherapy and bone
marrow transplantation (BMT). When bone marrow transplantation was first proposed, research
indicated the physician should give sufficiently high doses of chemotherapy to destroy all tumor
cells, while also destroying most of the patient’s other blood cells and immune system. The
physician would then rebuild the lost immune system through a bone marrow transplant from a
matched donor.
BMT requires a donor whose tissue match is close to the recipient’s own tissue. Therefore, an
identical twin was assumed to be ideal. However, when an identical twin was the donor, the
therapy failed. This unexpected turn changed researchers’ understanding of this therapy.
Apparently, high-dose chemotherapy did not annihilate the cancer cells in this therapy. Instead,
such an outcome was the effect of the slightly foreign immune cells from the donor— not the
perfectly matched twin donors.
These results have prompted the hospital system to research other alternatives to combat this
disease. In 1998, the hospital system recruited Thomas Wagner, Ph.D., and his associates, three
senior scientists from Ohio University, to research other treatments that have yielded positive
results. The ORI program is comprised of three laboratories: cell, molecular, and developmental
biology. Scientists at ORI are attempting to use new knowledge of the detailed molecular
pathways navigated by tenacious cancer cells along with others utilized by the body’s immune
system that counteract their persistence to develop new cancer therapies. Because of their
specificity and selectivity, these potential new therapies hold the promise of providing an
effective means of treating cancer with few side effects.
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Successes Treating Cancer
One of the most promising ORI clinical trials is Cellular Tumor Vaccine Therapy. This therapy,
now in Phase II clinical trials, has proven effective in some patients with melanoma and renal
cell carcinoma. This vaccine is effective because it presents the tumor’s “signature” to T cells (a
subpopulation of white blood cells of the patient’s immune system), stimulating them to generate
“killer” T cells called Cytotoxic T Lymphocytes (CTLs), which can attack and destroy tumor
cells wherever they might be situated within the body.
Because the surprising results from identical twin donors suggest that the truly curative aspect of
present therapy is immunological, both ORI and the Children’s Hospital are attempting to apply
a modification of ORI’s successful “vaccine” immunotherapy to pediatric leukemia. This CTL
treatment, unlike the current treatment for pediatric leukemia, does not require high doses of
chemotherapy. With one simple infusion, it gives the child a less painful treatment alternative to
destroy tumor cells.
Research Proposal Benefits
Through a cooperative program in children’s cancer research, the GHS Children’s Hospital and
ORI hope to discover an immune therapy treatment for pediatric leukemia that is less painful and
more successful than are current treatments.
The Challenge
ORI and its Basic Research Program are equipped with the latest instruments and facilities for
state-of-the-art cancer research. Its three divisions are guided by outstanding, visionary senior
medical researchers. Unfortunately, supporting staff and medical research associates are limited,
which restricts the number of research projects that can be undertaken and, subsequently, the
number of cancers for which new therapy can be developed.
A generous gift from B.K. and Frances Bryan seeks to address these limitations. Their gift has
initiated The New Hope Fund, which will house both an endowment and funds for immediate
use. The New Hope Fund will support new therapy team efforts to research specific cancer cures,
the first of which will be pediatric leukemia. Funds generated will provide stipends for 1)
research associates committed to curing pediatric leukemia and other targeted cancers and (2) the
costly supplies and equipment required for their work. The GHS Office of Philanthropy &
Partnership is seeking people who wish to be Visionary Philanthropists with the hospital system
in this project. The New Hope Fund is visionary. Funds will be used for innovative research
directed toward a more effective and less painful treatment. This project provides an opportunity
for compassionate and bold philanthropists to be added to this quest to benefit those in need
within the greater Greenville community, as well as throughout the world.
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Our Approach
Because our first patient group involves children with a significantly impaired immune system,
the ORI plans to simulate steps in an immune response to a vaccine in the laboratory rather than
within the patient. Once CTLs have been generated in the laboratory, they will re-introduce
billions of these “killer” T cells into the patient by intravenous infusion. In turn, it is hoped that
this reintroduction will generate an immune response against leukemia cells.
Since this approach is significantly different from ORI’s present vaccine therapy, the institute
must first confirm the soundness of this approach by way of animal studies. In these studies,
research associates at GHS and ORI will fuse mouse leukemia cells with mouse dendritic cells.
This process will generate mouse dendritomas to present the tumor “signature” of the leukemia
cells to mouse T cells. Mouse T cells will be removed from the experimental mice and incubated
with these dendritoma “vaccine” cells in a culture in ORI’s Cell Biology laboratory. The CTLs
against leukemia so generated will be expanded for several weeks.
These laboratory generated, anti-leukemia CTLs will be infused back into mice that have been
seeded with high levels of leukemia to mimic children with advanced leukemia. This step will
help determine if the therapy can effectively eliminate disease cells. If these experiments indicate
such therapy to be effective, the ORI will then apply to the FDA to initiate a Phase I clinical trial
to test children who have failed standard therapy. If these initial trials and follow-up Phase II
trials prove successful, the ORI and Children’s Hospital may then begin applying this less
devastating approach to the initial treatment of childhood leukemia.
Our Results
Dr. Wagner and his colleagues have been extremely successful at Greenville Hospital System,
having filed 20 patents and having completed the first Phase I clinical trial developed solely in
South Carolina. The hospital system is also one of a few targeted drug development sites
designated by the National Cancer Institute in the Southeast sponsoring early phase clinical
trials. The ORI team is currently investigating and developing novel therapies for melanoma,
breast, renal cell, and prostate cancers.
Request for Support
Mouse studies have already been initiated in the ORI to test this hypothesis. We hope to have
supporting data in the coming months that will document success in the lab. However, this
venture cannot be possible without the support of additional community Visionary
Philanthropists.
The New Hope Fund presents a visionary revenue pool that creates exploratory research
opportunities to find cures for today’s illnesses. To be successful, however, it needs the
commitment of a core group of philanthropists who will provide their financial support to this
effort. In all, this collaborative project, to be known as the New Hope Fund for Pediatric
Leukemia Research, requires a total of $1.3 million, over a five-year period. The fund needs up
to 13 philanthropists who will commit to a gift in the range of $20,000-$25,000 per annum for
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five years. Because of your considered support in this vision, children in Greenville with
Leukemia will have access to a treatment option more effective and less painful years before the
rest of the world.
Closing
As you consider your gift, keep in mind the plight of children who have cancer. Can we stop the
pain that current treatments inflict? As community leaders and philanthropists, will you do all
you can to support new and innovative research to help all our children lead better lives? Cancer
treatments are being developed in Greenville that have the potential to benefit generations to
come throughout the entire world.
Appendix
Initial Budget
Year 1 ..........................................................$530,000
Year 2 ..........................................................$130,000
Year 3 ..........................................................$205,000
Year 4 ..........................................................$205,000
Year 5 ..........................................................$205,000
Total for project .......................................$1,275,000
Year 1 and 2 expenses cover the salary/benefits and supplies of two medical research associates
to perform the initial mouse studies required. In addition, year one expenses include the purchase
of Cell Sorter required in meeting FDA regulations for this work. As we approach Year 3, we
will need a part-time medical director to oversee patient treatment initiatives. At the three-year
mark, we expect to have 10 to 15 patients enrolled in Phase I clinical trials. These trials will
evolve into Phase II trials that will evoke interest and financial support through application to the
National Cancer Institute (NCI), foundations, and other granting agencies to bring this treatment
approach to market.
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