Cancer vaccines are a form of immunotherapy that can help educate the immune system about what cancer cells “look like” so that it can recognize and eliminate them.
Vaccines have proven effective in preventing diseases caused by viruses and bacteria. Since the first vaccine was developed more than 200 years ago, they have prevented some of the twentieth century’s deadliest diseases and have helped save hundreds of millions of lives globally.
In the case of diseases caused by viruses (e.g., measles, polio, and smallpox) and bacteria (e.g., diphtheria, tetanus, and tuberculosis), vaccines work by exposing people to a weakened or inactivated version of the threat. This enables their immune system to identify these threats according to their specific markers—known as “antigens”—and mount a response against them. These vaccines typically work best in the preventive setting, when an individual is given the vaccine before being infected by the bacteria or virus.
In the case of cancer, however, the situation is more complicated for several reasons (more below) and this has made it more difficult to develop vaccines to either prevent or treat cancer. In particular, unlike bacteria and viruses, which appear foreign to our immune system, cancer cells more closely resemble our normal, healthy cells. Furthermore, each individual’s tumor is in some sense unique and has its own distinguishing antigens. As a result, more sophisticated approaches are necessary to develop effective cancer vaccines.
Preventive Cancer Vaccines
Viral infections are responsible for the development of several cancers and preventive vaccines play an important role in reducing risk. For instance, cervical cancer and head and neck cancer can be caused by human papilloma virus, or HPV, whereas liver cancer can be caused by hepatitis B virus or HBV. Several vaccines have been developed that can prevent HBV and HPV infection and, as a result, protect against the formation of HBV- and HPV-related cancers. Four of these preventive cancer vaccines have been approved by the U.S. Food and Drug Administration (FDA).
Therapeutic Cancer Vaccines
Each individual’s tumor is in some sense unique and has its own distinguishing antigens. As a result, more sophisticated cancer vaccine approaches are necessary.
Fortunately, tools now exist that enable doctors to identify targets on patients’ tumors that can help distinguish cancer cells from their normal cells. Sometimes these targets are normal proteins that are produced at abnormally high levels by cancer cells, such as prostatic acid phosphatase (PAP) that is often overexpressed by prostate cancer cells. Taking advantage of that insight, the sipuleucel-T vaccine was developed and was approved by the FDA in 2010 for the treatment of patients with advanced prostate cancer. Virus-derived proteins expressed by virus-infected cancer cells offer another promising source of markers that can be targeted through vaccines.
Another exception is Bacillus Calmette-Guérin, or BCG, a tuberculosis vaccine that acts as a general immune stimulant. In 1990, BCG became the first immunotherapy of any type to be approved by the FDA and is still used for the treatment of early-stage bladder cancer.
Personalized Neoantigen Vaccines
In contrast to normal-yet-overexpressed proteins like PAP, tumors also display unique targets that arise as a result of mutations. These are referred to as neoantigens (“new antigens”) and they are expressed exclusively by tumor cells and not by any of a patient’s healthy cells. With neoantigen vaccines, therefore, it is conceivable that immune responses could be directed precisely against patients’ tumor cells while sparing their healthy cells from immune attack, thus possibly preventing side effects.
In addition to the previously mentioned vaccines, several types of neoantigen vaccines are currently being evaluated, both alone and in combination with other treatments, in a variety of cancer types in clinical trials.
There are currently four vaccines that are approved by the FDA that can help prevent cancer, in addition to two FDA-approved vaccines for the treatment of cancer:
Preventive Cancer Vaccines
- Cervarix®: a vaccine approved for use in preventing infection by the two strains of HPV that cause most cervical cancers, HPV types 16 and 18; can help prevent the development of HPV-related anal, cervical, head and neck, penile, vulvar, and vaginal cancers
- Gardasil®: a vaccine that protects against infection by HPV types 16, 18, 6, and 1; can help prevent the development of HPV-related anal, cervical, head and neck, penile, vulvar, and vaginal cancers
- Gardasil-9®: a vaccine approved for the prevention of infection by HPV types 16, 18, 31, 33, 45, 52, and 58, and for the prevention of genital warts caused by HPV types 6 or 11; can help prevent the development of HPV-related anal, cervical, head and neck, penile, vulvar, and vaginal cancers
- Hepatitis B (HBV) vaccine (HEPLISAV-B®): a preventive vaccine that protects against infection by the hepatitis B virus; can help prevent the development of HBV-related liver cancer
Therapeutic Cancer Vaccines
- Bacillus Calmette-Guérin (BCG): a vaccine that uses weakened bacteria to stimulate the immune system; approved for patients with early-stage bladder cancer
- Sipuleucel-T (Provenge®): a vaccine composed of patients’ own stimulated dendritic cells; approved for prostate cancer
Side effects can vary according to the type of cancer vaccine—and what exactly it targets—and can also be influenced by the location and type of cancer as well as a patient’s overall health. With current cancer vaccines, sometimes these can cause the immune system to target healthy cells that also express those same target proteins, which can cause off-target side effects. Patients should consult their care team to gain a better and fuller understanding of the potential risks and side effects associated with specific cancer vaccines.
The side effects most commonly associated with currently approved cancer vaccines are: anorexia, back pain, chills, fatigue/malaise, fever, flu-like symptoms, headache, joint ache, myalgia, nausea, and neuralgia.
For information regarding the side effects associated with cancer vaccines and other immunotherapy approaches, please refer to our Immunotherapy Side Effects page.
Throughout CRI’s history, we have supported a variety of basic research aimed at improving our understanding of the principles behind vaccines and strategies to identify the most promising vaccine targets as well as translational and clinical efforts that seek to use these insights in the development of cancer vaccines for patients in the clinic.
Some of the most important contributions made by CRI scientists in the area of cancer vaccines include:
- In 1959, Lloyd J. Old, M.D., CRI’s founding scientific and medical director, showed that the tuberculosis vaccine Bacillus Calmette-Guérin (BCG) could inhibit tumor growth in mice. Then, in 1980, CRI-funded grantee Alvaro Morales, M.D., of Queen's University (Canada), demonstrated that BCG can prevent bladder cancer recurrence in human patients. The FDA approved the use of BCG for superficial bladder cancer in 1990.
- In 2001, CRI grantee Ian H. Frazer, M.D., of the University of Queensland, made important breakthroughs regarding human papilloma virus (HPV)-targeting vaccines that paved the way for the development of the first preventive cervical cancer vaccine, Gardasil®.
- In 2009, former CRI grantees Sjoerd van der Burg, Ph.D., and Cornelis Melief, M.D., Ph.D., both of the Leiden University Medical Center found that a vaccine composed of human papilloma virus (HPV) long peptides could produce durable complete responses in some women with HPV-16+ pre-cancer of the vulva.
- In 2012, CRI predoctoral fellow Matthew Vesely, Ph.D., and CRI grantee Robert Schreiber, Ph.D., highlighted how next generation sequencing could be used to characterize tumor neoantigens for the development of vaccines.
- In 2017, CRI grantees Sacha Gnjatic, Ph.D., of the Icahn School of Medicine at Mount Sinai, and Kunle Odunsi, M.D., Ph.D., of the Roswell Park Comprehensive Cancer Center, found that vaccines against NY-ESO-1 were associated with improved survival in patients with aggressive ovarian cancer. This was based on work throughout the 2000s involving a number of CRI-funded scientists—including Maha Ayyoub, M.D., Ph.D., Nina Bhardwaj, M.D., Ph.D., Dirk Jaeger, M.D., Elke Jaeger, M.D., Alexander Knuth, M.D., Lloyd J. Old, M.D., Gerd Ritter, Ph.D., and Danila Valmori, Ph.D.—advanced our understanding and development of NY-ESO-1-targeting vaccines in a variety of cancers.
Currently, CRI is funding the following grantees whose research involves cancer vaccines:
- Susan E. Klaeger, Ph.D.—a CRI-Hearst Foundations Fellow at the Broad Institute of Harvard and the Massachusetts Institute of Technology (MIT)—is aiming to decipher the rules that govern the intracellular processing of (neo-)antigens and their presentation on the surface of cells, in order to Improve our ability to create personalized vaccines for cancer patients.
- Marc Joseph Lajoie, Ph.D.—a CRI postdoctoral fellow at the University of Washington—is exploring the use of nanoparticles to deliver “intel” to the immune system about what cancer “looks like,” which will hopefully help to improve the success of vaccine strategies.
- Andrew I. Flyak, Ph.D.—a CRI postdoctoral fellow at the California Institute of Technology—is analyzing patients whose immune systems naturally eliminated hepatitis C virus (HCV) infections, in order to aid the development of a potential HCV vaccine.
- Michael J.Hogan, Ph.D.—a CRI postdoctoral fellow at the Children’s Hospital of Philadelphia—is investigating an “alternative” method through which antigens are presented via the MHC II pathway, in order to aid the development of more effective cancer vaccine strategies.
Additionally, CRI is currently providing funding support for the following clinical trial involving a cancer vaccine:
- A phase I/II trial (NCT03164772) combining two checkpoint inhibitors with a cancer vaccine in patients with advanced lung cancer. This trial is being led by Jhanelle Gray, M.D., of the Moffitt Cancer Center, Joshua Sabari, M.D., of New York University (NYU) Langone Medical Center, and Jonathan Thompson, M.D., of the Medical College of Wisconsin.
I can’t overstate how lucky I am to have been in the exact right place, at the exact right time, to get a spot in the nivolumab trial.
Lymphoma | Diagnosed 2010
Read My Story
Alexandra Boussommier, Ph.D.
Massachusetts Institute of Technology
Postdoctoral Fellow | 2014
View Funding Directory