Physicians at HonorHealth Research Institute have begun a clinical trial of a new, potentially more powerful, treatment for fighting advanced melanoma, using the immune system's dendritic cells to create a vaccine.
The vaccine, DOC1021, is a first-in-class immunotherapy for those patients whose melanoma is: "refractory," meaning it is resistant to current treatments, and is either "unresectable," meaning it cannot be removed by surgery, or "metastatic," meaning it has spread to other organs.
"Vaccines have historically been limited in cancer. They're often not potent enough for patients with metastatic disease," said Justin Moser, M.D., the clinical trial's principal investigator and an associate clinical investigator in the Research Institute's Oncology Research Division, where he specializes in melanoma.
"I hope this approach will be able to overcome the limitations of prior vaccines and work for patients with metastatic disease," said Dr. Moser, who also is a Clinical Assistant Professor at the University of Arizona College of Medicine-Phoenix, and an Associate Research Professor at Arizona State University's John Shufeldt School of Medicine and Medical Engineering.
HonorHealth Research Institute is one of just a handful of facilities nationwide offering this clinical trial, "Dendritic Cell Immunotherapy for Refractory Melanoma," which uses DOC1021, also known as dubodencel, made by Houston-based Diakonos Oncology.
Melanoma is an aggressive cancer originating from melanocytes, which create protective pigmentation. While most commonly originating in the skin (cutaneous melanoma), it also can arise in mucosal surfaces, such as those that form a protective lining of the ears, nose, lungs, mouth, and digestive tract.
What are dendritic cells?
The vaccine is based on a patient's dendritic cells, a type of immune cell that helps the body recognize and respond to threats. Dendritic cells act as the immune system's messengers, informing the immune system's cancer killing T cells and B cells. In this therapy, dendritic cells are combined with mRNA and proteins derived from the patient's biopsied tumor cells to target the cancer.
Previously, this vaccine has been used successfully in another clinical trial to treat glioblastoma (GBM), the most common type of brain tumor.
Joseph Georges, D.O., Ph.D., a Neurosurgeon at Scottsdale Neurosurgery Specialists, based in the Bob Bové Neuroscience Institute on HonorHealth's Scottsdale Osborn Medical Center campus, worked on the pre-clinical studies supporting a clinical trial that uses similar vaccine technology to fight GBM.
Initial phases of that trial resulted in some patients surviving more than two and three years without adverse effects, well beyond the average 15-month survival for GBM, said Dr. Georges, whose academic interests are focused on improving brain tumor therapies. He serves as an Assistant Professor of Clinical Practice at ASU's school of medicine, and an Adjunct Professor in ASU's School of Molecular Sciences and Bioengineering.
"We started seeing promising results, and indications that it might work against other cancers.
Melanoma was high on the list because it has been shown that modifications in the immune system could more effectively treat that cancer," Dr. Georges said.
For example, another clinical trial offered by HonorHealth Research Institute uses TILs (Tumor Infiltrating Lymphocytes), which are immune cells that can already recognize a cancer, but often become weak or are evaded by the cancer. TIL cellular therapy involves removing hundreds of these cells from the patient's tumor and, in a lab, enhancing their abilities and multiplying them, then infusing the patient with billions of new cancer-killing immune cells.
How TIL and dendritic therapies differ
Unlike TILs, which can already recognize the cancer, the dendritic-based vaccine directly trains the immune system to recognize and fight the cancer, similar to how the immune system is trained to fight the flu or any other vaccine-vulnerable disease. Also, unlike TILs, which commonly require chemotherapy and additional medicines to prepare and support the immune system, DOC1021 is designed to activate the patient's own immune system without these additional treatments.
"The vaccine trains the immune cells to recognize the cancer as if it were an infection," Dr. Moser said.
Because this vaccine is double-loaded with both mRNA and protein from the tumor, Dr. Georges said, "We generate an almost 10-fold increase in the immune response," compared to using only the mRNA or protein materials.
Researchers are expanding this vaccine approach to fight other cancers, such as pancreatic cancer, as well.
Our immune system has the hardware to attack and kill cancer cells. It's just that cancers get really good at fooling our immune system and preventing our immune system from targeting and killing them. Vaccines help educate our immune system to target and kill cancer cells, when previously those cells were trying to hide."
Dr. Joseph Georges, D.O., Ph.D., Neurosurgeon at Scottsdale Neurosurgery Specialists
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