CRI’s Dr. Jill O’Donnell-Tormey Explains Five Things You Need to Know About Cancer Vaccines

Vaccines had been effective at preventing viral and bacterial-borne viruses for two hundred years before the first cancer vaccine was approved by the US Food and Drug Administration (FDA) in 2010. Today, there are four preventative cancer vaccines and two therapeutic cancer vaccines.

Recently, the Cancer Research Institute’s (CRI) CEO and Director of Scientific Affairs Jill O’Donnell-Tormey, PhD, took some time to answer a few questions about the history of cancer vaccines, CRI’s impact on the production of cancer vaccines, and what role they can play in improving immunotherapy treatment outcomes for patients.

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Can you describe how cancer vaccines work, specifically within an immunotherapy context? 

Cancer vaccines work by stimulating the body to recognize a cancer cell as foreign and destroy it. They work in the same way as the many vaccines we receive throughout life to prevent common illnesses like measles or flu, training the immune system to identify and destroy harmful germs and cells.

Can you describe any recent progress on cancer vaccine development that CRI has been involved in? 

Cancer vaccines have seen decades of development, much of which has been disappointing. In the early 2000s, through its Cancer Vaccine Collaborative (CVC), CRI undertook a committed effort to develop an effective therapeutic vaccine for cancer.

These efforts centered on systematically testing whether various vaccine compositions and routes of administration could deliver a productive and integrated immune response consisting of antigen specific CD4 and CD8 T cells and antibodies.

While this multi-pronged immune response could be measured in patients, it did not lead to significant clinical responses. At the time it became clear that two important factors needed to be addressed if we were going to be successful in generating an effective therapeutic vaccine: the antigenic target and the immune suppression that followed immune activation.

The more recent successes of vaccines to treat both melanoma and pancreatic cancer suggest that the conclusion reached by CRI’s CVC investigators was on point. These two separate trials, which were reported within the past year, used mRNA technology to deliver a personalized neoantigen (targets found specific to each patient’s cancer) vaccine in combination with a checkpoint blockade that blocks the tumor’s ability to suppress an immune response against it.

What was the set of circumstances that led to the development of the first cancer vaccine? Was this a project that had been in the pipeline for a long time, or did the science rapidly accelerate leading to the development of the first cancer vaccine? 

In the 1970s Dr. Harald zur Hausen hypothesized that human papillomaviruses (HPVs) might be a causative agent for cervical cancers. However, the first HPV vaccine, which serves as a preventative vaccine for HPV-related cancers, was not approved by the US Food and Drug Administration (FDA) until 2006.

Although the HPV vaccine is considered a cancer vaccine, it is somewhat of a misnomer because it is actually a vaccine against a virus that subsequently causes cancer. The immune response generated by the vaccine is not against the cancer but rather against the virus. If the virus is eliminated the cancer is prevented.

The FDA has approved several vaccines to prevent HPV infection, which target high-risk HPV strains responsible for nearly all cervical cancers and linked to some throat, anal, and other cancers.

The Gardasil HPV vaccine uses virus-like particles, which resemble the HPV shell, and were developed by CRI-funded scientist Dr. Ian Fraser and his collaborators.

Can you describe the types of cancer vaccines, and what functions they serve? (Preventative, therapeutic, and personalized neoantigen) 

Preventative vaccines can protect healthy people from infection and disease. The childhood vaccinations we get for measles and chicken pox are preventative vaccines. The only preventative cancer vaccines are for those caused by viruses. These include the HPV vaccine, which protects against infection by the human papillomavirus, and the Hepatitis B vaccine, which protects against the hepatitis B virus (HBV) that causes liver cancer. A preventative vaccine will only work if a person gets the vaccine before they are infected by the virus.

Therapeutic vaccines are meant to activate a patient’s immune system to fight and control an already-established infectious pathogen. Therapeutic cancer vaccines are given to people who already have cancer. Cancer cells contain markers called antigens that are either present at lower levels or not present at all.

Therapeutic vaccines help the immune system recognize these cancer antigens and destroy the cancer cells displaying them. Vaccines can deliver cancer antigens in a variety of forms that include proteins, peptides, DNA, RNA, viral vectors, microbial vectors, and antigen-presenting cells. Currently, most therapeutic cancer vaccines are only offered through clinical trials. However, in 2010, the FDA approved sipuleucel-T (Provenge) as a therapeutic vaccine for advanced prostate cancer. This is a personalized vaccine that removes a patient’s white blood cells, which are trained in a laboratory to recognize prostate cancer cells and infused back into the patient.

Another approved therapeutic vaccine uses a weakened bacteria called Bacillus Calmette-Guérin (BCG) that is injected into the body. This weakened bacterium activates the immune system to treat early-stage bladder cancer.

Recently, the FDA has granted a breakthrough therapy designation to a personalized mRNA therapeutic vaccine that encodes up to 34 so-called neoantigens in combination with a PD-1 checkpoint blockade following resection of high-risk melanoma. Neoantigens are antigens that are completely unique to the cancer cells of a given patient. Another mRNA vaccine encoding neoantigens in pancreatic cancer has been shown to delay cancer recurrence when combined with a PD-1 checkpoint and chemotherapy in pancreatic cancer patients after surgery.

Much of the recent clinical results from mRNA vaccines stem from research that had begun prior to the COVID epidemic. The knowledge accrued on mRNA technology and safety profiles seen in early clinical testing of these cancer vaccines jump-started the research on the mRNA COVID vaccines. The cancer vaccine reach is one reason COVID vaccines were able to be developed at such an accelerated pace.

Where do you see possibilities for improvement within cancer vaccine development? For example, are there particular cancers that current immunotherapy treatments fail to adequately address? 

In the past decade checkpoint blockade immunotherapy has revolutionized cancer treatment. Checkpoints are now approved to treat a variety of cancers, but only a minority of cancer patients benefit. Checkpoints work in what is considered ‘hot’ tumors that already have an abundance of T cells within the tumor microenvironment by reversing immune suppression and allowing the T cells to carry out their effector function of killing tumor cells.

One way to increase response to checkpoints is to turn ’cold’ tumors that lack a T cell infiltrate into hot tumors. A way to do this is with a therapeutic cancer vaccine that would attract T cells into the tumor bed. An obvious place for continuing research is to develop a vaccine for the tumor types that do not respond to monotherapy checkpoint blockade. This includes pancreatic, ovarian, and prostate cancers. 

Another near-term use of cancer vaccines is to use them to treat patients who have successfully responded to surgery and/or chemotherapy and appear to be tumor-free but are at a high risk of recurrence. Since cancer vaccines have been proven safe and devoid of serious adverse events, they are a likely addition to the treatment regimen as they could elicit a productive immune memory that would enable the immune system to respond to and eliminate any future recurrence.

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CRI is looking forward to sharing new cancer vaccine updates as they become available. Cancer vaccine development is an exciting and promising avenue in the maturation of cancer immunotherapy treatment that will help make a world immune to cancer.