One of the difficulties with vaccines, particularly cancer vaccines, is knowing just which target to hit, as cancer cells, even those of the same type or from within the same tumor, can have differences in the proteins on their surfaces. Gradalis' approach to this problem is to create an autologous cancer vaccine--a vaccine created from a sample of the patients' own tumors--and has seen people with advanced disease still alive almost three years after treatment.
In the therapeutic vaccine, known as FANG, the patients' cells are manipulated to produce granulocyte-macrophage colony-stimulating factor (GMCSF), which stimulates the immune system, and RNAi (a strand of genetic material), which blocks the growth factors that suppress the immune system, and then given back to the patient in an injection just under the skin.
Gradalis has completed a Phase I study of its vaccine, which enrolled 46 patients with advanced disease, including melanoma, colorectal, breast, ovarian and hepatocellular cancers. Of these, 27 patients received the vaccine monthly for between one and 12 months, and the results are published in Molecular Therapy.
The treatment was well-tolerated, and 23 patients achieved stable disease within two months of starting treatment. The median survival in treated patients was 554 days, compared with 132 days in those patients in the study who did not get the vaccine, but who had standard of care treatment. Seven vaccinated patients were still alive at follow up, at almost three years (940 days) survival, and these were all patients who showed a positive immune system response.
"The pronounced survival benefit achieved by FANG in patients with multiple tumor types is quite remarkable, and randomized Phase 2 trials are currently underway verifying these results," said Dr. John Nemunaitis, executive medical director of the Mary Crowley Cancer Research Centers and chief medical officer and co-founder of Gradalis. "The benefit is likely attributed to the triad approach, which is designed into the vaccine to maximize its effect. FANG is not only manufactured using each individual's tumor to assure exposure to the appropriate antigens, but it also activates immune cells and prevents production of proteins that tumors use to avoid detection by the immune system. I believe that this triad approach may one day make it possible to turn cancer into a manageable chronic disease for many patients."
Because it has a personalized approach, FANG may be suitable for a range of cancers, and could provide an option for people with advanced and previously untreatable disease. Gradalis is carrying out Phase II trials in patients with advanced ovarian cancer, advanced melanoma and advanced colorectal cancer with liver metastases, and clinical trials in children with Ewing's sarcoma.
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