Vaccine Therapy for Cancer
How does the immune system work?
The immune system is a network of organs, cells, and proteins that work to protect our bodies from foreign invaders such as infections. The immune system fights against pathogens like bacteria, viruses, parasites, and fungus that the body has been exposed to. The immune system also fights against cells already in the body that have changed due to illness, such as cancer. White blood cells, also called leukocytes, seek out these foreign pathogens and destroy them. There are two different types of leukocytes, B lymphocytes, and T lymphocytes. B lymphocytes seek out the pathogens and T lymphocytes destroy the pathogens. B lymphocytes also make antibodies. Antibodies are proteins in the body that fight infections that the body has already been exposed to.
What is a cancer vaccine?
Most of us have received vaccines for infectious diseases, such as measles and hepatitis. These vaccines use weakened or killed viruses, bacteria, or other germs to start an immune response in the body. Cancer vaccines are designed to work in a similar manner, teaching the immune system to recognize, attack, and destroy cancer cells. Normally, when foreign cells enter the body (for example, when an infection occurs), the immune system responds to the invasion and clears the body of the foreign cells. Unlike infectious cells, cancer cells are not recognized as foreign by the body. Instead, the immune system thinks the cancer cells are part of the normal body and do not mount an immune response against the cancer. Cancer vaccines allow the immune system to recognize cancer cells as foreign and get the immune system to attack the cancer cells. Cancer vaccines are one way to use the body’s immune system to fight cancer.
How do non-cancer vaccines work?
Most commonly, vaccines are used to prevent infections. By introducing inactivated or killed forms of a virus or bacteria to the immune system before an infection actually occurs, the immune system is "primed" to recognize potential infections. Antibodies that are specific for the vaccine are produced in the body and allow for a very rapid response to potential infections by the virus or bacteria that the vaccine was made to target. In this way, actual infections can be quickly recognized by the immune system and eliminated before a significant infection can occur.
How do cancer vaccines work?
A true cancer vaccine contains cancer cells, parts of cells, or pure antigens. The vaccine increases the immune response against cancer cells that are already present in the body. This is in contrast to vaccines for diseases that are designed to prevent infection. Cancer vaccines spur the immune system into recognizing tumor cells as foreign invaders so that they may be destroyed by the immune system. Tumor cells often express distinct antigens known as tumor-associated antigens (TAAs). One of the greatest problems with developing cancer vaccines has been that most TAAs are also present in normal cells. Because the immune system sees these antigens as self-antigens, no immune response is mounted. If the immune system can be taught to recognize the TAAs as foreign, an immune response can be mounted against the tumor. Several TAAs have been identified that are found in specific types of cancers, but not in normal cells. By targeting these TAAs with cancer vaccines, cancer vaccines can cause the immune system to attack cancer cells while leaving normal, healthy cells largely intact. Currently, cancer vaccines targeting cancers of the breast, prostate, liver, kidney, pancreas, and lung, melanoma, and certain types of leukemias and lymphomas are in clinical trials.
Are there any vaccines that prevent cancer?
Some cancers are known to be caused by viral infections. Infection with human papilloma virus has been shown to be a cause of cervical cancer, as well as some head and neck, penile, anal, vulvar, and vaginal cancers. Hepatitis B and C viruses are known to cause liver cancer. Vaccines that prevent infection from these viruses would help to prevent these cancers. While these vaccines may prevent cancer, these are not cancer vaccines. These vaccines are directed against viruses, rather than cancer itself.
Do cancer vaccines work?
There have been a number of clinical trials testing cancer vaccines. Thus far, there is only one cancer vaccine found to improve overall survival. Sipuleucel-T (Provenge®) is approved for use in some men with metastatic prostate cancer. It stimulates an immune response to prostatic acid phosphatase (PAP), an antigen present on most prostate cancers. In a clinical trial, Provenge increased the survival of men with hormone refractory metastatic prostate cancer by about 4 months. The vaccine is customized for each patient. The exact mechanism of action of sipuleucel-T is unknown, but it is likely that the APCs that have taken up PAP-GM-CSF stimulate T cells to kill tumor cells that express PAP.
Another viral therapy approved for use is called talimogene laherparepvec and it is used in the treatment of melanoma that can't be removed with surgery. The drug is a weakened form of Herpes Simplex Virus Type 1. The medication is injected directly into the melanoma tumor on the skin or in a lymph node. This makes the cancer cells to burst and die. This medication has not been shown to improve overall survival.
A viral therapy called Bacillus Calmette-Guerin (BCG) is a weakened strain of Mycobacterium bovis. It works against cancer as a biologic response modifier. This means that it is able to trigger the immune system to attack tumors. BCG is thought to work by stimulating an immune response and causing inflammation of the bladder wall that destroys cancer cells within the bladder.
Cancer vaccines remain an important and growing area of cancer research. A number of trials are being done to test these vaccines. A number of key questions and areas of research remain. We are still quite a ways away from incorporating cancer vaccines into the routine care of cancer patients. The possibility of using the body's own immune system to destroy cancer cells remains an appealing possibility and results of early trials are promising. Research into new ways of treating cancer, such as cancer vaccines, remains an important part of the search for a cure.
Cancer Research Institute. Cancer Vaccines: Preventive, Therapeutic, Personalized.
American Cancer Society. Cancer Vaccines and their Side Effects. 2020.
A controlled trial of a human papillomavirus type 16 vaccine. Koutsky LA, Ault KA, Wheeler CMet al. N Engl J Med. 2002 Nov 21;347(21):1645-51.
Sipuleucel-T immunotherapy for castration-resistant prostate cancer. Kantoff PW, Higano CS, Shore ND, et al. New England Journal of Medicine 2010; 363(5):411–422
Cancer Vaccines: Between the Idea and the Reality. Finn OJ. Nat Rev Immunol. 2003 Aug;3(8):630-41. Reviewed by Ryan P. Smith, MD
A phase I trial of cytotoxic T-lymphocyte precursor-oriented peptide vaccines for colorectal carcinoma patients. Sato Y, Maeda Y, Shomura H et al. Br J Cancer. 2004 Apr 5;90(7):1334-42.
Cancer Vaccine Triggers Immune System to Recognize Melanoma. ASCO 1998.
Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells.Su Z, Dannull J, Heiser A er al. Cancer Res. 2003 May 1;63(9):2127-33.
Immunopharmacologic analysis of an autologous, hapten-modified human melanoma vaccine. Berd D, Sato T, Maguire HC Jr et al. J Clin Oncol. 2004 Feb 1;22(3):403-15. Epub 2003 Dec 22.
Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): a trial of the Eastern Cooperative Oncology Group. Kaufman HL, Wang W, Manola J et al. J Clin Oncol. 2004 Jun 1;22(11):2122-32.
Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: overall results of a randomized trial of the Southwest Oncology Group. Sondak VK, Liu PY, Tuthill RJ et al. J Clin Oncol. 2002 Apr 15;20(8):2058-66.
Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial. Jocham D, Richter A, Hoffmann L et al. Lancet. 2004 Feb 21;363(9409):594-9.
FDA Access Data Sheet. Gardasil ®. 2015. Found at: http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM111263.pdf
National Institute of Health. National Cancer Institute. Cancer Vaccines. 2018. Found at: http://www.cancer.gov/about-cancer/causes-prevention/vaccines-fact-sheet