All vaccines work by training your immune system to defend your body against foreign invaders or abnormal cells that pose a threat. There are two main types of cancer vaccines:

• Preventive Cancer Vaccines
• Therapeutic Cancer Vaccines

These vaccine types can protect against cancer in different ways.

Preventive Cancer Vaccines

Most people are familiar with preventive vaccines, the more conventional vaccine type. They boost your body’s natural ability to defend against foreign invaders, like bacteria and viruses. Well-known examples include the flu shot and vaccines for measles or the COVID-19 virus.

You might wonder, “Can vaccines prevent cancer?” The answer is “Yes, some can.” They can reduce your risk of cancer by protecting against certain viral infections that can cause the disease.

The two currently approved preventive cancer vaccines are:

• Human Papillomavirus (HPV) Vaccine
  • This vaccine prevents against the HPV virus, which is so common that nearly all sexually active people get it at some point in their life — unless they get the HPV vaccine. Chronic HPV infection can cause several types of cancer, including cervical cancer, head and neck cancers, anal cancer, penile cancer, vaginal cancer, and vulvar cancer. The HPV vaccine greatly reduces risk of these cancers.
• Hepatitis B Vaccine
  • Hepatitis B is a liver disease caused by the hepatitis B virus (HBV). It ranges in severity from a mild illness, lasting a few weeks (acute), to a serious long-term (chronic) illness that can lead to liver cancer. Getting the hepatitis B vaccine reduces risk of liver cancer.

Therapeutic Cancer Vaccines

Doctors use therapeutic cancer vaccines to treat cancer after it occurs rather than to prevent it. Therapeutic vaccines work by training your body to protect itself against its own damaged or abnormal cells, including cancer cells.

Therapeutic cancer vaccines expose your immune system to molecules, called antigens, that are associated with a specific type of cancer. These vaccines enable the immune system to recognize and destroy the cancer cells. Therapeutic cancer vaccines consist of specific antigens combined with another immune system trigger called an adjuvant.

Therapeutic cancer vaccines can:

• Stop a tumor from growing or spreading.
• Destroy cancer cells still in the body after treatments like surgery or radiation therapy.
• Keep cancer from coming back after treatment.

What are the challenges for therapeutic cancer vaccines?

• Cancer cells produce molecules that suppress the immune response. Even if a vaccine can switch on immune cells, those immune cells may not be able to enter the tumor area. And if they do enter, they may be immediately shut down.
• Cancer cells start out as normal cells and don’t look as threatening to the immune cells. This makes it harder for the immune system to detect what to attack.
• It can be hard to find antigens that are cancer-specific. If the antigen exists on both normal and abnormal cells, the vaccine will attack the normal cells too. This causes unwanted side effects.
• The tumor may be too big. Large tumors have more immune-suppressive cells, which can negate the power of the immune cells triggered to attack them. Because of this, vaccines may be combined with other treatments.
• Some people have weakened immune systems. Older people and many others — especially people with cancer — might not be able to respond well enough to a vaccine. Even if the immune cells receive the vaccine’s signal, they cannot mount a strong enough attack.

Approved Therapeutic Cancer Vaccines

Several therapeutic cancer vaccines have been approved by the U.S. Food and Drug Administration (FDA) and are already in use for different cancers:

• Prostate Cancer Vaccine
  • Sipuleucel-T (Provenge®) is used for the treatment of people whose prostate cancer has metastasized (spread). Provenge is created by removing some immune cells, exposing them to a molecule from prostate cancer cells, and then infusing them back into the body. It has been shown to extend survival in people with metastatic prostate cancer.
• Bladder Cancer Vaccines
  • Bacillus Calmette-Guérin (BCG) is used to treat early-stage bladder cancers. It is made from inactivated tuberculosis bacteria. When BCG is put into the bladder as a liquid through a catheter (a thin, flexible tube), it helps stimulate immune system cells, which then attack the bladder cancer cells.
  • Nadofaragene firadonevec (Adstiladrin®) is approved for treatment of early-stage bladder cancers that have progressed despite BCG therapy. It consists of an engineered, weakened virus that activates an immune response in the bladder. Like BCG, it is delivered into the bladder through a catheter.
• Melanoma Vaccine
  • T-VEC (Imlygic®) is an oncolytic virus-based vaccine (see below) that is used to treat advanced melanoma that cannot be completely removed with surgery. It is made of a virus that has been genetically modified to promote an anticancer immune response.

Therapeutic Cancer Vaccine Clinical Trials

Many clinical trials (research studies) are testing vaccines in different cancers. Some of the most notable include:

• Pancreatic Cancer Vaccine
  • Memorial Sloan Kettering Cancer Center (MSK) has been testing an mRNA vaccine against pancreatic cancer. The vaccines are custom-made for every person. Doctors hope the vaccine can reduce the risk of pancreatic cancer returning after the main tumor is removed by surgery. This potential treatment came through an MSK collaboration with BioNTech, which developed the Pfizer-BioNTech COVID-19 vaccine. The vaccine is given in combination with checkpoint inhibitors, drugs that “release the brakes” on the immune system and allow it to mount a stronger attack against cancer.
• Head and Neck Cancer Vaccine
  • MSK is participating in a clinical trial testing a therapeutic vaccine against HPV-associated head and neck cancers. (These cancers developed from an HPV infection.) The vaccine is based on proteins found in HPV that also are expressed in the infected host cells that become cancerous.

Improving Therapeutic Cancer Vaccines

Researchers continue to make progress in the field of cancer vaccines. Advances in genetic sequencing methods have made it possible to find better cancer-specific antigens for designing vaccines. Cancer cells pile up DNA mutations (changes) at a high rate. The mutations create new, abnormal proteins in the cancer cells, which scientists call neoantigens. These neoantigens are providing new and better targets for cancer vaccines, such as the pancreatic cancer vaccine.

Combination Cancer Therapies

A cancer vaccine by itself may not be enough to curb tumor growth. As tumors develop, they produce molecules that actively prevent immune cells from doing their job. That’s why, increasingly, scientists think that combination cancer therapies — with vaccines as one component — may be the best approach. Many cancer vaccines are being combined with checkpoint inhibitors.

Oncolytic Virus-Based Vaccines

Oncolytic viruses are viruses, which may or may not be genetically modified in some way, that can infect and kill cancer cells. Vaccines using these viruses are appealing because they are very good at attracting immune attention, functioning in some ways like antigen and adjuvant in one.

Intratumoral Therapies (In Situ Vaccines)

In situ vaccination essentially uses the tumor that the patient has as a vaccine. It involves injecting immune-activating drugs into the tumor, causing the tumor itself to provide the antigens to activate the immune response. This strategy is being tested using various immune-activating drugs, including oncolytic viruses, bacteria, antibodies, and other molecules.