From Plant Virus to Cancer Vaccine

Development of a vaccine for COVID-19 has been a common headline over the past year. A vaccine stimulates the body’s immune system to protect it against invading microorganisms such as viruses. But vaccines could also stimulate an immune response against cancer. The idea of a vaccine for cancer is not new. But there are differences between viruses and cancer that make creation of a cancer vaccine particularly challenging.

Components of a vaccine

The two main components of a vaccine are antigen and adjuvant.

Antigen is the immunologist term for molecules recognized by your immune system as foreign when they enter your body. There are two broad types of antigens. Foreign antigens are introduced from outside of the body, such as bacteria or viruses like influenza and COVID-19. Self-antigens originate within the body and are part of autoimmune diseases. Cancer antigens are in between foreign and self-antigens.

The other component, adjuvant, is what stimulates the immune response against the antigen. “You can think of the antigen as the target, and the adjuvant as the alarm that tells the immune system, ‘Wake up, pay attention, we have a problem’,” explains Steven N. Fiering, PhD, a researcher in the Immunology and Cancer Immunotherapy Research Program at Dartmouth’s and Dartmouth-Hitchcock’s Norris Cotton Cancer Center. “Every vaccine has these two components. Both are important and have to be doing their job in order to be a good vaccine.”

Virus vaccines versus cancer vaccines

Viruses often have very easily recognized antigens. The COVID-19 vaccines, for example, target the Spike protein, which sticks out from the virus molecule. Once Spike proteins are coated in antibodies produced by the immune system from vaccination, they can no longer interact with the receptor that allows the virus to invade cells. So, the infection is stopped.

Tumor cells, however, don’t have easily recognized antigens like the Spike protein. “The proteins in tumor cells are mostly normal, but there are some that aren’t quite right and those are the antigens that can be recognized by the immune system,” says Fiering. “But they’re not big immune targets like the Spike protein, they’re quite subtle.”

One strategy of developing a vaccine is to identify one antigen as the target, such as the Spike protein, and ignore the rest of the virus. The other strategy is to use a killed or weakened virus that contains any and all antigens, no matter what they are. “In our lab, we’re not trying to identify specific antigens,” says Fiering. “We’re interested in the whole tumor as the source of the antigen because it’s got everything and we don’t need to go through the big challenge of figuring it out. Asking questions about what the tumor has and doesn’t have in it takes time and is difficult and expensive. We’re saying any antigens that are relevant to this cancer are here in this tumor, so just use the tumor as the antigen. It keeps things simple.”

Window of opportunity

Fiering recently published findings of this approach used in mouse models of ovarian cancer. The study found a good response to vaccination in preventing tumor growth during remission. “Our idea is that the period of remission that’s common in ovarian cancer after surgery and chemotherapy is the perfect time to try to develop an immune response against the tumor,” says Fiering. “There is very little tumor, which is easier for the immune system to handle, and the woman is relatively healthy. There is a window of opportunity in treating ovarian cancer that currently isn’t being utilized. It’s something we want people to start thinking about because it’s a therapy option for a challenging cancer and does not disrupt clinical standard of care.”

For the study, Fiering’s team used mouse cancer cells to model human ovarian tumor tissue. They killed the tumor with high-dose radiation to use as the antigen.

The adjuvant, a plant virus called cowpea mosaic virus (CPMV), is the focus of a collaboration between Fiering and Nicole Steinmetz, PhD, from University of California San Diego. “For reason’s we’re starting to understand, CPMV is very immuno-stimulatory, which is the job of the adjuvant,” says Fiering. “However, an adjuvant needs to stimulate the immune system in the right way for the desired effect. In infectious diseases, you want an immune response that produces protective antibodies. In tumors, you want a response from T cells, which are immune cells that can directly kill tumor cells. Adjuvants help direct whether you get antibody response or T cell response and CPMV stimulates the right pathways to get a good T cell response.”

The next phase

While Fiering is optimistic that side effects would be minimal as they are with most vaccines, clinical trials would be needed to determine the safety profile of the treatment. Those trials are the next goal of the project.

Fiering has joined with a team of scientists and entrepreneurs to form biotech company, Mosaic ImmunoEngineering, Inc. that is planning to develop CPMV as a biological drug for the treatment of cancer. The company’s goal is to complete the regulatory requirements for clinical development including manufacturing and toxicology studies and to begin Phase I clinical trials by early 2022.
 
“Virtually nobody is thinking of using a plant virus as a therapeutic in humans. We are in a position to lead the charge,” notes Fiering, who is encouraged by an increase in research around vaccination for tumors. “People are starting to see more value in this approach and we are happy to be among the first really exploring its potential.”