Vaccine Trial Update

GM-CSF Secreting Autologous Tumor Cell Vaccine Trial Update

John M. Goldberg, MD

Dana-Farber Cancer Institute

Children’s Hospital, Boston

In our 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 the section titled, GM-CSF Secreting Autologous Tumor Cell Vaccines,

"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.

The main contact for this trial, for both pediatric and adult patients, is Dr. John Goldberg. Click here to e-mail him a note.

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.

The Liddy Shriver Sarcoma Initiative has helped fund this study. See our Funded Research webpage. The ClinicalTrials.gov listing of this study can be viewed by clicking here.