By Sara Bondell - March 01, 2021
As COVID-19 swept the world, it didn’t feel like there was any end in sight. The pressing question on everyone’s mind: When will there be a vaccine?
The past didn’t instill much confidence. After all, an Ebola vaccine wasn’t approved by the U.S. Food and Drug Administration until the end of 2019, more than five years after the virus’s latest epidemic.
But then, in December, the FDA granted emergency use of a COVID-19 vaccine manufactured by Pfizer. A week later, the Moderna vaccine received the same approval.
And while that quick turnaround may have seemed miraculous to some, it wasn’t. It was all thanks to cancer research.
“When we talk about the COVID-19 vaccine, this is not new technology,” said Patrick Hwu, MD, president and CEO of Moffitt Cancer Center. “They could make this vaccine so quickly because they had already been doing this for cancer.”
Now the success of the vaccines is once again generating excitement about developing a similar inoculation for cancer. Moffitt is currently studying a vaccine that uses the same technology as the COVID-19 vaccine in lung cancer, and is opening a trial for head and neck cancer in the spring.
Most traditional vaccines, like the flu shot, use inactivated or weakened viruses that once injected into the body stimulate an immune response that can later protect against infection. There are also protein vaccines, such as the Hepatitis B and HPV vaccines, that deliver the part of the virus that stimulates a protective antibody response. Developing these vaccines is a complicated process that requires much time and money.
Vaccines based on Messenger RNA, or mRNA, do not have these problems. Instead of using the virus, they contain genetic material that instructs the body to develop defenses against future infection. These vaccines can be produced quicker and cheaper than traditional ones.
Development of the COVID-19 vaccine can be traced to the early 2000s and Hungarian scientist Katalin Karikó, who discovered a way to harness the power of mRNA to fight disease. Her work caught the eye of Ugur Sahin and Ozlem Tureci, co-founders of BioNTech, a German biotechnology company. They hired Karkió to continue her work on using mRNA to cure cancer.
While chemotherapy is the main weapon to fight cancer, it acts like an atomic bomb, killing healthy cells along with cancerous ones. Sahin and Tureci realized they could better fight the disease by harnessing the immune system, and they believed mRNA could get the job done.
As tumors grow, they express unique markers called neo-antigens that are not found on normal cells. By sequencing a tumor and finding the unique markers, the scientists believed they could create a vaccine to get the immune system to respond to those markers.
But progress on using mRNA vaccines in cancer treatment was slow. Then cases of a novel respiratory virus started popping up overseas, and mRNA technology was given new life. Once scientists were able to sequence this mysterious disease, they got to work. In fact, BioNTech was one of the companies that partnered with Pfizer to develop its COVID-19 vaccine.
‘As personalized as you can get’
The success of the COVID-19 vaccine took mRNA technology from the laboratory to the spotlight, and Moffitt researchers are now preparing for a first-of-its-kind cancer vaccine trial this spring.
The study, which is part of a larger national trial, is headed by Kedar Kirtane, MD, a medical oncologist in Moffitt’s Head and Neck Oncology Program. It will determine the safety and efficacy of an mRNA vaccine for head and neck cancer patients with recurrent or metastatic disease in combination with pembrolizumab, a checkpoint inhibitor.
“We will take a tumor sample and sequence it to look for the unique cancer markers. Then we will create a vaccine to target them,” said Kirtane. “It really is as personalized as you can get.”
While there currently are two approved immunotherapy treatments for head and neck cancers, only about 20% of patients respond. Vaccine trials like this one will hopefully open the opportunity to satisfy a critical unmet need in this patient population.
“The biggest thing thus far that has made me happy about the COVID-19 vaccines is the safety,” Kirtane said. “RNA vaccines have been studied for a while, but we haven’t seen mass use of them. So, the fact there’s all this data suggesting safety really is the first big thing.”
Moffitt’s Thoracic Oncology Program is also participating in a multicenter study evaluating the safety and efficacy of the addition of a mRNA vaccine to combination immunotherapy treatment for non-small cell lung cancer patients with metastatic disease.
In the future, there may also be a place for mRNA vaccine technology in cervical cancer treatment. Previously, many pharmaceutical companies were studying DNA-based vaccines to treat high-grade cervical cancer caused by human papillomavirus (HPV). While the vaccines showed some level of efficacy, the administration of the vaccine required an uncomfortable procedure called electroporation, which uses electrical pulses to create temporary pores in cell membranes.
“Companies that started with DNA-based technology are moving towards mRNA platforms because it really allows for a simpler delivery,” said Anna Giuliano, PhD, founding director of Moffitt’s Center for Immunization and Infection Research in Cancer. “This is a trend we are seeing and it started even before the COVID-19 pandemic.”
For most cancers, researchers don’t know what antigen to target to illicit an immune response. But when it comes to cancers caused by HPV, they know exactly which two proteins to target, making a vaccine a potential powerful treatment tool. Vaccines can be DNA-based, mRNA-based or protein based.
“When it comes to treating cervical cancer, there is a tremendous need for a vaccine,” said Giuliano. “The majority of cases occur in the poorest countries and treating those cases in cost-effective ways is a huge problem. This could fill an important medical need.”
Giuliano has received a grant from the National Cancer Institute to implement three trials to help prevent cervical cancer in Latin America. One of the trials will study the efficacy of a protein-based vaccine, which Giuliano says could easily be transferred into a mRNA vaccine if needed.
Regardless of how they’re made, cancer experts believe vaccines could have a major impact on fighting the disease. The important thing is to keep studying them to determine if they need to be combined with other treatments and find the best timing for administration.
"The first step is to generate a lot of immune cells that can recognize the cancer, but we may need other therapies to get the other steps to happen. Those immune cells need to travel to the cancer and once they’re there they have to attack it."- Dr. Patrick Hwu, President and CEO
“The first step is to generate a lot of immune cells that can recognize the cancer, but we may need other therapies to get the other steps to happen,” said Hwu. “Those immune cells need to travel to the cancer and once they’re there they have to attack it.”
Vaccines can also be used as adjuvant therapy, given to patients after their tumors have been surgically removed to lower the risk that microscopic disease left behind can cause a recurrence.
The success of the COVID-19 vaccine has created new awareness of potential cancer treatments, and Hwu says he hopes this stimulates more vaccine research.
“There are so many ways to make a vaccine and the first few ways we tried didn’t work. So, people started throwing their hands up and saying, ‘Oh, we can’t make cancer vaccines,’” he said. “But a cancer vaccine could potentially be among the most cost-effective methods of preventing recurrences and the high costs of cancer care.”
“We have to keep trying. Don’t give up on cancer vaccines.”