Early Grants from the Initiative
Award to Dr. Mary Louise Keohan
As a results of or first Team Sarcoma's participation in Cycle Zydeco 2003, we raised $14,000 to sponsor the research of Dr. Mary Louise Keohan at the Herbert Irving Comprehensive Cancer Center at Columbia University and the New York Presbyterian Hospital.
Dr. Keohan's publications include "What is angiogenesis and how does it play a role in cancer treatment?" and "What is immunotherapy and what role does it play in cancer treatment?".
Elizabeth Shriver Memorial Research Awards to Study Sarcoma
These three awards, totaling $75,000, were announced in 2004. See the press release for additional information.
Dr. Matt van de Rijn of Stanford University is the recipient of a $25,000 Elizabeth Shriver Memorial Research Award. He is one of the few researchers in the country to use gene chips on sarcomas. He will use the sarcoma cell lines generated by Dr. Fletcher to analyze thousands of genes in these tumors. The technique is called DNA microarray and allows one to put the tumor DNA on a chip containing DNA from essentially all known genes; if the tumor DNA binds, it means that gene is present in the tumor. One can then tell if key genes in the tumor are absent (allowing the tumor to grow unchecked) or abnormal. Once these abnormal genes are found, researchers can attempt to block their effect using various molecules — thus searching for so-called "molecular targets" for new therapies. "Again, the Sarcoma Foundation of America and the Elizabeth Shriver Award will have a significant impact on our knowledge of how sarcomas grow, and on future sarcoma research," Thornton said. "This is the type of study that can lay the groundwork to find the magic bullet, though it will likely take years." Dr. van de Rijn published an ESUN article based on his work.
Dr. Frederic Barr of the University of Pennsylvania is also the recipient of a $25,000 Elizabeth Shriver Memorial Research Award. He is well known for his work on gene fusions in rhabdomyosarcoma (RMS), so he is well familiar with the complex genes in this tumor. Most of the alveolar type of RMS, a childhood tumor, form when two genes are abnormally stuck together (PAX and FKHR genes). For unknown reasons, some alveolar RMS lack this finding and yet still form and grow. "In this grant, Dr. Barr will try to determine how and why some rhabdomyosarcomas do not have the usual gene fusion, which causes abnormal growth," explained Thornton. "Perhaps by learning this, some mysteries of RMS can be unraveled. Often by testing the exceptions to the rule one can learn a great deal and perhaps find another molecular target." Dr. Barr published an ESUN article based on his work.
Dr. Lisa Wang of Baylor College of Medicine in Houston is also the recipient of a $25,000 Elizabeth Shriver Memorial Research Award. She had been involved in studying a group of people with a genetic syndrome that results in a certain germ-line mutation in all their normal cells. The gene, called RECQL4, is a DNA helicase (enzyme) that functions to maintain genomic stability. When it is mutated there is genetic instability and an increased risk of osteosarcoma. She will now test whether or not the same mutations are a common feature of all osteosarcomas. If this gene is very common in osteosarcomas, it may then become a target for therapy in the future. "It is possible that this rare genetic syndrome may lead to finding a key gene in this bone tumor, and the Sarcoma Foundation of America and Elizabeth Shriver Award is critical to getting this investigation done and an answer known. Only by following such leads is progress made," said Thornton.
Funding a Study of Tumor Lysate-Pulsed Dendritic Cell Vaccine
In January 2005, the Brian Morden Foundation and the Liddy Shriver Sarcoma Initiative awarded a $50,0000 grant for research on a vaccine to treat recurrent and relapsed Ewing's Sarcoma, a rare cancer. The vaccine was developed by a team of oncology specialists at the University of Michigan Medical Center led by Dr. James Geiger, with Dr. John E. Levine and Dr. Raymond Hutchinson as co-investigators. This study continued an initial Phase I Clinical Trial funded by the National Institutes of Health that Dr. Geiger and his team initiated. Funds from the Brian Morden Foundation and the Liddy Shriver Sarcoma Initiative, in addition to grants from the University of Michigan, will allowd doctors to offer a new alternative to patients whose traditional chemotherapy and radiotherapy have failed. See the press release.
Funding a GM-CSF Secreting Autologous Tumor Cell Vaccine Trial
in 2005, the Liddy Shriver Sarcoma Initiative donated $50,000 to Dana-Farber Cancer Institute to support a vaccine study for clear cell sarcoma (CCS), alveolar soft part sarcoma (ASPS), and pediatric melanoma. Dr. John Goldberg and Dr. David Fisher co-directed this study. See the press release.
A 2006 Update on the GM-CSF Study
In the article, Clear Cell Sarcoma and Alveolar Soft Part Sarcoma, that appeared in the August 2005 Issue of ESUN, Dr. Karen Albritton and I stated:
In an effort to harness the immune response against melanoma for therapeutic purposes, investigators at the Dana-Farber Cancer Institute have been developing GM-CSF secreting autologous tumor cell vaccines. These vaccines are created by taking a piece of tumor removed during surgery, breaking the tumor up into single cells in a special laboratory and then treating the cells to make a vaccine that will stimulate the immune system to attack other tumors when the vaccine is given back to the patient. The treatment of the cells in the laboratory includes using adenoviral mediated gene transfer, which adds a new gene to the cancer cells. Adenoviruses are common respiratory pathogens and can cause illnesses similar to a cold in normal people. In the laboratory, researchers can trick adenovirus into carrying a helpful gene while losing its ability to cause an illness. The gene that is transferred to make the vaccine is GM-CSF, a powerful cytokine that stimulates the immune system. The cells are then given enough radiation so that they will never grow when given back to the patient, but not enough to completely destroy them. They are then injected into the patient on a regular schedule. The actual injections are like childhood vaccinations that go under the skin or into the muscle. It is hoped that the cancer cells that have been made to secrete the hormone GM-CSF will cause the immune system to attack the cancer in other parts of the body.
This vaccine will be used to treat patients with CCS, ASPS, pediatric renal carcinoma and children with melanoma in the near future at the Dana-Farber Cancer Institute, but it is not yet available. Children with melanoma have been studied with interferon, as two pediatric oncology groups recently published experiences using interferon, but few trials include Stage IV pediatric patients (Chao, Schwartz et al. 2004; Navid, Furman et al. 2005). While GM-CSF secreting vaccines are not proven to cure patients with advanced melanoma, they tend to have little toxicity and may be safe in patients with CCS and ASPS. An additional hurdle in treating patients with this vaccine strategy is that they must go to the treatment center where the vaccine is being offered to undergo surgery, and then remain there to receive their vaccinations. This hurdle is comparable to that for most pediatric oncology protocols and protocols for rare sarcomas, which are not widely available and generally require patients to go to large cancer centers for treatment.
The trial discussed in this last paragraph is now underway at the Dana-Farber Cancer Institute and this brief note is an update regarding it. This Phase 1 clinical trial is formally called, "Phase I Trial of Vaccination with Autologous, Lethally Irradiated Tumor Cells Engineered by Adenoviral Mediated Gene Transfer to Secrete GM-CSF in Adult and Pediatric Patients with Advanced Clear Cell Sarcoma, Translocation Associated Renal Cell Carcinoma, Alveolar Soft Part Sarcoma and Children with Stage IV Melanoma." It uses a previously established technique of tumor cell vaccination.
The scientific rationale involves surgically removing a patient’s own (autologous) tumor cells and genetically altering them so that they secrete a protein called granulocyte-macrophage stimulating factor (GM-CSF). The "GM-CSF secreting tumor cells " are then irradiated which prevents them from being able to grow, but allows them to still secrete GM-CSF. Once injected under the patient’s skin, these vaccine cells secrete GM-CSF, which attracts cells of the immune system to the site. In theory, the immune system cells become activated and "see" the tumor cells as "foreign." The immune system cells attack the tumor cells at the site as well as recruit other cells of the immune system to attack tumor cells elsewhere in the body.
It is important to understand that this is a Phase I trial, meaning that the principal aims of the study are to demonstrate the safety and feasibility of the approach. It is possible that patients treated on this protocol will have no benefit from the therapy, and will be exposed to the risk of an experimental treatment.
A team of physician-scientists at DFCI/HCC has worked for over ten years in the development of cancer vaccine strategies utilizing GM-CSF secreting tumor vaccines. Observations from the previous studies conducted here have demonstrated that this cancer vaccine elicits a strong immune response in patients at the site of injection and in some cases stimulates an immune response against the cancer cells in other parts of the patient’s body. In the current study, we have incorporated the experience that we have accumulated in several cancer vaccine studies in patients with metastatic melanoma, lung cancer and ovarian cancer.
About 36 people will take part in this study through the Dana-Farber/Harvard Cancer Center. Fifteen of these patients will be children with melanoma, and the other 21 patients will be adults and children with either alveolar soft part sarcoma, clear cell sarcoma or a kind of kidney cancer that children get, known as translocation associated renal cell carcinoma.
This trial is only available to patients who come to the Dana-Farber Cancer Institute for evaluation, surgery and study treatment. Patients from all over the world are eligible to receive the study treatment provided they are able come to Boston. No specific funding is available at this time for patients who must travel to Boston or for patients whose insurance coverage will not pay for surgery and hospital visits. The total time from surgery to completion of the trial is approximately 3 months. Following surgery, patients receive vaccination once weekly for 3 weeks and then every other week for 3 weeks. Patients must be deemed healthy enough to participate in this clinical trial, as it is an experimental therapy and it is possible that very ill patients will become sicker before they are able to complete the trial.
Please note that it is necessary to have the patient’s physician consult with Dr. Goldberg to determine if he or she might be considered eligible for the trial. Thank you for your interest in this exciting new clinical trial, as we continue our work to learn more about the treatment of these very challenging diseases.