Cancer vaccines are showing promise. Here’s how they work.

Typically, vaccines help protect us against diseases. Cancer vaccines are a different kind of vaccine. They can be used to treat people with cancer. These treatments have been years in development, with many failures, but now they are beginning to show promise.

In the past decade, technological innovations such as genome sequencing have allowed scientists a closer look at cancer cells and their genetic abnormalities. This allows them to design vaccines that target specific targets. Stephen Schoenberger, a cellular immunologist at the La Jolla Institute for Immunology, San Diego, said that they have been learning more about the immune system and how it recognizes, destroys, and destroys a patient with cancer.

Cancer vaccine research is still in the nascent stages, says Nina Bhardwaj, a hematology and medical oncology expert at the Icahn School of Medicine at Mount Sinai in New York. She says that early results from clinical trials of vaccine candidates against a variety cancers are encouraging.

While the goal is to develop vaccines that kill cancer cells, some scientists are also working on vaccines that could prevent high-risk individuals from getting cancer.

What are cancer vaccines?

The purpose of all vaccines, be it a cancer vaccine or COVID-19 vaccine, is to educate the immune system and provide a preview of the target that needs to be identified and destroyed to keep the body safe. The COVID-19 vaccine teaches the immune system what the SARS-CoV-2 virus looks like so when the pathogen infects, immune cells can quickly locate the virus and kill it. A cancer vaccine teaches immune cells what a tumor cell looks like, so they can seek out and destroy them. The ability of a vaccine against cancer to teach the immune system is what makes it different from other immunotherapies. These therapies use therapeutic agents like cytokine proteins or antibodies and include strategies such as genetically engineering patients’ immune cells to fight cancer.

Experts says that cancer vaccines can potentially destroy cancer cells that might have survived other treatments, stop the tumor from growing or spreading, or stop the cancer from coming back.

Some therapeutic vaccines against cancer rely on the removal of immune cells called dendritic cell from patients and then exposing them in the lab to key proteins taken from the patient’s cancer cells. These educated cells are then given back to the patient in the hope that they will stimulate and train other immune cell types, such as T cells to detect and destroy cancer. Christopher Klebanoff, a medical oncologist at New York’s Memorial Sloan Kettering Cancer Center, said

T cell can perform one of the most remarkable tricks in biology. They have a receptor that can recognize and bound to proteins on tumor cells’ surfaces, much like a lock fits a door. He says that once they are bound, the T cells use mechanical force to puncture the tumor cell and kill it.

But “vaccines haven’t been very good at generating the quality and quantity of T cells necessary to eliminate large tumors,” Bhardwaj says. It’s ideal to vaccinate when the tumor is small, she says. Researchers often combine vaccines with drugs that increase the anti-tumor immune response to boost their effectiveness.

Vaccine-makers now are increasingly relying on mRNA technology–also used to create COVID-19 vaccines–to instruct dendritic cells in a patient’s body to produce the tumor-specific proteins or peptides that will generate an immune response. Some vaccines can be used to prevent cancer by teaching the body how to kill cancer-causing viruses such as hepatitis B or human papillomavirus. This will prevent an infection that could lead to a tumour.

How do scientists create cancer vaccines?

All cancer-treating vaccines rely on proteins, called tumor-associated antigens–a molecule that triggers an immune response when it’s either more plentiful on the surface of cancer cells compared to healthy ones, or exists in an abnormal or mutated form. T cells recognize these antigens and kill the cancerous cells once they “see” them.

Cancer biologists identify these tumor antigens with sophisticated sequencing technology that spots specific differences between the DNA or RNA of a healthy cell versus a cancer cell. Schoenberger says the trick is to identify which mutations will trigger a T-cell response and make a good target for vaccine development.

His group chooses antigens based upon the patient’s response. Schoenberger says that by studying blood samples from patients, “we’re looking to see what the patient’s immune system has chosen among the tumor-expressed mutants to target.” To create vaccines, he identifies antigens specific to a patient’s tumor cells. Other researchers search for antigens that can be shared between people with a particular type of cancer or between different types.

Vaccines designed to target molecules that are overproduced by cancer cells but also present in smaller amounts in healthy cells tend to have limitations and may not initiate an effective immune response. Lisa Butterflied, a cancer immunologist at the University of California San Francisco, says that this has been a major hurdle. Inducing autoimmunity is another risk. This is when the immune system attacks healthy cells and causes bodily disorders that can be difficult to treat. Now, more efforts are being made to find neoantigens, which are targeted molecules that are specific for tumors.

Are there approved vaccines to treat cancer and how they do work?

In 2010, the U.S. Food and Drug Administration approved the first therapeutic cancer vaccine, called Sipuleucel-T, to treat advanced prostate cancer. It targets an antigen called prostatic acids phosphatase. It is present in normal prostate cells, but it is more common in cancerous ones. Clinical trials showed patients vaccinated with Sipuleucel-T lived about four months longer, although their tumors remained the same size.

Other vaccines that have been approved against viruses like hepatitis B and human papillomavirus are also considered cancer vaccines because they prevent viral infections that could one day lead to liver, cervical, head, and neck cancers.

These preventative vaccines work by generating antibodies against the virus, and to the best of our knowledge, not a very effective T cell response, Klebanoff says. “That’s why they can’t be used as a therapy against cancer.”

What cancer vaccines are in the pipeline?

Scientists are testing dozens of cancer vaccines, often in combination with other immunotherapies. They are targeting different types of cancers, including skin, bladder, prostate and pancreatic.

Last week, vaccine-maker Moderna announced that its candidate mRNA vaccine against stage three or four melanoma showed a 44 percent reduction in risks of skin cancer recurrence or death among patients who received both the vaccine and a Merck drug called Keytruda, which boosts the immune response against cancer cells, compared to those who took only Keytruda. Moderna’s personalized mRNA vaccine trains the immune system to produce T cells against 34 cancer-specific antigens. Although the results of this phase two clinical trial are yet to be peer-reviewed, the company, along with Merck, is planning a larger phase three trial in 2023 to test the vaccine’s safety and efficacy.

Cancer immunologist Olivera Finn at the University of Pittsburg is testing a preventative vaccine that can be given at a pre-cancer stage, when an individual develops benign growths called polyps–which are not dangerous but can turn malignant–inside their colon. The vaccine targets an abnormal form of a protein called MUC1 produced by some non-malignant colon polyp cells. It led to a 38 percent reduction in recurrence within three years of vaccinating nearly 50 individuals with advanced polyps. Finn states that if you don’t get a new prick, you are not at increased risk for colon cancer.

Scientists need to find out why certain people are more responsive to vaccines than others, and how long they will be protected. The hope is that more vaccine candidates will progress to phase three randomized clinical trials, where their safety and effectiveness can be evaluated in large groups of patients.

What challenges do scientists foresee?

Despite the renewed excitement in developing and testing cancer vaccines, given technological advances, some scientists like Klebanoff remain skeptical. Klebanoff wonders if vaccines will ever be powerful enough to cause tumor shrinkage in clinically meaningful ways. He also wonders whether other strategies like engineering patient’s T cells, so-called CAR-T cell therapy, so they can better recognize cancer cells, will prove more effective. His research group uses this approach. He is eager to see the results of ongoing vaccine clinical trials.

Since therapeutic vaccines are often tested in patients with advanced cancer who have had their tumor surgically removed and have been through chemotherapy or radiation, their immune systems are really beat up, Schoenberger says. The vaccines may not work as well in this stage of the disease. He says that we will need to identify the patients and clinical settings where cancer vaccines are most effective.

Cancer vaccines are still in the early phases of testing and refining, Butterfield cautions. There is still much work to do on both the preventative and therapeutic vaccines side.