Every day more than 1,600 Americans die from cancer. Most of them have cancer that can’t be cured with traditional methods — surgery, radiation and chemotherapy. The father of Evanthia Galanis, M.D., was one of them.
“My father would have better treatment options today,” says Dr. Galanis, chair of the Department of Molecular Medicine at Mayo Clinic in Rochester and the Sandra J. Schulze Professor. “Research has led to the availability of very effective melanoma treatments, including immunotherapy. My father always encouraged me to be the best I could be. Every time I see a patient with cancer for whom we can’t offer good options, I think of him, and my commitment to decreasing the burden of cancer and eliminating it altogether is re-energized. I’m more determined to find answers as a result of that very difficult personal experience. I know my father’s legacy makes me a better oncologist and researcher.”
From fellow to virotherapy P.I.
Dr. Galanis’ research is focused on developing viral gene and cell therapies to treat cancer. She has been the principal investigator in multiple phase I and II gene therapy and virotherapy trials in solid tumors (ovarian cancer, glioblastoma, renal cell carcinoma, colorectal cancer, melanoma and pancreatic cancer).
She believes that ongoing trials could result in viral therapy products being approved for cancer treatment in the next several years. Many viruses are drawn to cancer cells, which grow and replicate more quickly than normal cells. Virotherapy harnesses viruses’ cancer-cell-killing ability to attack cancer cells while sparing normal cells. Mayo Clinic has explored treating cancer with gene therapies and viruses for about 25 years, making it one of the oldest cancer gene therapy and virotherapy programs in the country. Dr. Galanis was there from the start — as a hematology/oncology fellow.
“When you understand what’s wrong with a cancer cell, you can design a gene-based treatment to repair the defect or convert the abnormally behaving cell to one that behaves like normal cells,” says Dr. Galanis. “That led to my interest in gene therapy — using genetic material to treat disease — and trials to introduce genes in tumors. Today we have much better ways to deliver genetic material to cells; we also can use viruses to deliver genetic material that replicates and kills cancer cells. This is a welcome alternative to chemotherapy, which isn’t selective and can be crude for and highly toxic to patients.”
The measles virus is one of the most promising viral platforms. It has shown to be safe, generates good immune response from the tumor, and can be engineered to carry genes and retargeted to be more specific against certain types of cells. In the early 2000s, Mayo Clinic researchers delivered a weakened strain of the measles virus to laboratory mice with ovarian cancer. Their tumors shrank by 80 percent. To test that approach in humans and more quickly move ideas to the clinic, Mayo Clinic created a vector production facility — one of the only academic sites in the world capable of manufacturing clinical-grade engineered viruses for patient use.
First-in-human measles virus trials
Dr. Galanis led the first-in-human clinical trials in which 36 patients with recurrent ovarian cancer were treated with homegrown measles strains. Patients treated with higher doses of the viruses achieved a median overall survival of 27 months — more than twice as long as the expected median survival in these heavily pretreated patients who had failed multiple chemotherapy regimens. The vaccine provided remarkable results on other cancers in the lab, eliminating tumors in almost every model tested.
A five-year, three-site randomized phase II trial is now comparing measles virus treatment for ovarian cancer with the treating physician’s chemotherapy of choice. In addition to efficacy, the virotherapy is much less toxic than chemotherapy, resulting in better quality of life for patients.
More recently, Dr. Galanis led the first human trial of stem cell delivery of a cancer-killing virus. The phase I/II trial uses a small amount of a patient’s fat tissue to generate stem cells at Mayo’s Human Cellular Therapy Laboratory that are then infected with measles virus. The cells are subsequently infused back to the patient. The infected stem cells help lead the virus to tumor sites. With a grant from the National Cancer Institute, the trial recently expanded the number of patients to assess efficacy and treatment impact on survival. If the trial succeeds, the way physicians deliver viruses to cancer patients could change drastically.
When viruses destroy cancer cells, they release hundreds of infectious virus particles to kill the remaining tumor. The infected cells also secrete chemicals that trigger the anti-tumor immune response. This ability to kill cancer cells and recruit immune cells to join the fight makes viruses a potentially potent treatment for advanced cancers that don’t respond to other therapies.
Dr. Galanis is exploring ways to strengthen this immune response to cancer by combining the measles virus with an antibody that unleashes the immune system — a combination of virotherapy and immunotherapy. In mice with malignant brain tumors, this combination therapy significantly increased survival, leading to cures in 60 percent of the animals.
In further exploration of these encouraging results, Dr. Galanis’ laboratory has modified the measles virus to express genes that significantly enhance the immune response to the tumor, which Dr. Galanis describes as a form of vaccination against cancer. The first-ever phase I clinical trial with one of these designer viruses is about to launch in patients with metastatic breast cancer in partnership with Mayo Clinic’s Specialized Program of Research Excellence (SPORE) in breast cancer.
A new standard of care
With the first-in-human testing of the measles vaccine for ovarian cancer, first-in-human stem cell delivery of a virus and novel combination virotherapy-immunotherapy approaches under her belt, Dr. Galanis remains laser-focused on rapid translation of lab work to trials.
“Viruses represent an innovative way to treat cancer, and clinical activity is very promising,” says Dr. Galanis. “Some of the leading efforts in the world in virotherapy are happening at Mayo Clinic. We believe our trials will lead to viruses becoming incorporated to the standard of care. I’m honored to be part of a team in the Department of Molecular Medicine and the Cancer Center that can bring clinical and lab work together and move science forward to help our patients and change lives.”
This article was originally published in Mayo Clinic’s Alumni Magazine, Issue 4, 2018.
NOTE: The composite image is from the Mayo Clinic Viral Vector Production Laboratory.