Cancer Vaccines. An update
What is immune system? The immune system is a complex network of cells, tissues, organs, and the substances they make that helps the body fight infections and other diseases.
Antigens are substances that have the potential to cause the body to mount an immune response against them. They help the immune system determine whether something is foreign, or “non-self.” Normal cells in the body have antigens that identify them as “self.” Self antigens tell the immune system that normal cells are not a threat and should be ignored. In contrast, microbes are recognized by the immune system as a potential threat that should be destroyed because they carry foreign, or non-self, antigens.
Are cancer cells recognized by the immune system? Cancer cells can carry both self antigens as well as what are referred to as cancer-associated antigens. Cancer-associated antigens mark cancer cells as abnormal or foreign and can cause killer T cells to mount an attack against them.
However, several factors may make it difficult for the immune system to target growing cancers for destruction:
• Many cancer-associated antigens are only slightly altered versions of self antigens and therefore may be hard for the immune system to recognize.
• Cancer cells may undergo genetic changes that may lead to the loss of cancer-associated antigens.
• Cancer cells can evade anticancer immune responses by killer T cells. As a result, even when the immune system recognizes a growing cancer as a threat, the cancer may still escape a strong attack by the immune system
What are cancer vaccines?
Cancer vaccines belong to a class of substances known as biological response modifiers. Biological response modifiers work by stimulating or restoring the immune system’s ability to fight infections and disease. There are two broad types of cancer vaccines:
• Preventive (or prophylactic) vaccines, which are intended to prevent cancer from developing in healthy people
• Treatment (or therapeutic) vaccines, which are intended to treat an existing cancer by strengthening the body’s natural immune response against the cancer (9). Treatment vaccines are a form of immunotherapy.
• How do cancer preventive vaccines work?
• Cancer preventive vaccines target infectious agents that cause or contribute to the development of cancer. They are similar to traditional vaccines, which help prevent infectious diseases, such as measles or polio, by protecting the body against infection. Both cancer preventive vaccines and traditional vaccines are based on antigens that are carried by infectious agents and that are relatively easy for the immune system to recognize as foreign.
• Most preventive vaccines, including those aimed at cancer-causing viruses (hepatitis B virus and human papillomavirus), stimulate the production of antibodies that bind to specific targeted microbes and block their ability to cause infection.
What cancer preventive vaccines are approved?
Human papillomavirus (HPV) vaccines. Persistent infections with high-risk HPV typescan cause cervical cancer, anal cancer, oropharyngeal cancer, and vaginal, vulvar, and penile cancers. Three vaccines are approved by the US Food and Drug Administration (FDA) to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix. Gardasil and Gardasil 9 are approved for use in females ages 9 through 26 for the prevention of HPV-caused cervical, vulvar, vaginal, and anal cancers; precancerous cervical, vulvar, vaginal, and anal lesions; and genital warts. Gardasil and Gardasil 9 are also approved for use in males for the prevention of HPV-caused anal cancer, precancerous anal lesions, and genital warts. Gardasil is approved for use in males ages 9 through 26, and Gardasil 9 is approved for use in males ages 9 through 15. Cervarix is approved for use in females ages 9 through 25 for the prevention of cervical cancer caused by HPV.
Hepatitis B virus (HBV) vaccines. Chronic HBV infection can lead to liver cancer. The FDA has approved multiple vaccines that protect against HBV infection. Two vaccines, Engerix-B and Recombivax HB, protect against HBV infection only. Both vaccines are approved for use in individuals of all ages. Several other vaccines protect against infection with HBV as well as other viruses. Twinrix protects against HBV and hepatitis A virus, and Pediarix against HBV, poliovirus, and the bacteria that cause diphtheria, tetanus, and pertussis. Twinrix is approved for use in persons 18 years of age or older. Pediarix is approved for use in infants whose mothers are negative for the HBV surface antigen (HBsAg) and is given as early as 6 weeks of age through 6 years of age. The original HBV vaccine was approved by the FDA in 1981, making it the first cancer preventive vaccine to be successfully developed and marketed.
Cancer treatment vaccines?
In April 2010, the FDA approved the first cancer treatment vaccine. This vaccine, sipuleucel-T (Provenge), is approved for use in some men with metastatic prostate cancer. It is designed to stimulate an immune response to prostatic acid phosphatase (PAP), an antigen that is found on most prostate cancer cells. In clinical trials, sipuleucel-T increased the survival of men with a certain type of metastatic prostate cancer by about 4 months.
Unlike some other cancer treatment vaccines, sipuleucel-T is customized to each patient. The vaccine is created by isolating immune system cells called dendritic cells, which are a type of antigen-presenting cell (APC), from a patient’s blood through a procedure called leukapheresis. These cells are sent to the vaccine manufacturer, where they are cultured together with a protein called PAP-GM-CSF. This protein consists of PAP linked to a protein called granulocyte-macrophage colony-stimulating factor (GM-CSF). The GM-CSF stimulates the immune system and enhances antigen presentation
In October 2015, the FDA approved the first oncolytic virus therapy, talimogene laherparepvec (T-VEC, or Imlygic) for the treatment of some patients with metastatic melanoma that cannot be surgically removed. In addition to infecting and lysing cancer cells when injected directly into melanoma tumors, T-VEC induces responses in non-injected lesions, suggesting that it triggers an antitumor immune response similar to those of other anticancer vaccines.
Do cancer vaccines have side effects?
Before any vaccine is licensed, the FDA must conclude that it is both safe and effective. Vaccines intended to prevent or treat cancer appear to have safety profiles comparable to those of other vaccines (6). However, the side effects of cancer vaccines can vary among vaccine formulations and from one person to another.
The most commonly reported side effect of cancer vaccines is inflammation at the site of injection, including redness, pain, swelling, warming of the skin, itchiness, and occasionally a rash.
People sometimes experience flu-like symptoms after receiving a cancer vaccine, including fever, chills, weakness, dizziness, nausea or vomiting, muscle ache, fatigue, headache, and occasional breathing difficulties. Blood pressure may also be affected. These side effects, which usually last for only a short time, indicate that the body is responding to the vaccine and making an immune response, as it does when exposed to a virus.
Other, more serious health problems have been reported in smaller numbers of people after receiving a cancer vaccine. These problems may or may not have been caused by the vaccine. The reported problems have included asthma, appendicitis, pelvic inflammatory disease, and certain autoimmune diseases, including arthritis and systemic lupus erythematosus.
Can cancer treatment vaccines be combined with other types of cancer therapy?
Yes. In many of the clinical trials of cancer treatment vaccines that are now under way, vaccines are being given with other forms of cancer therapy. Therapies that have been combined with cancer treatment vaccines include surgery, chemotherapy, radiation therapy, and some forms of targeted therapy, including therapies that are intended to boost immune system responses against cancer.
A number of vaccines designed to treat specific cancers are currently under development. These include dendritic cell vaccines for metastatic renal cell carcinoma, glioblastoma, and metastatic hormone-refractory prostate cancer; autologous tumor cellvaccines for colorectal cancer and follicular lymphoma; anti-idiotype vaccines for lymphomas and some solid tumors; vaccines designed to stimulate an immune response against hormones required for the growth and survival of gastrointestinal malignancies; allogeneic vaccines for lung cancer; and a DNA-based vaccine for metastatic breast cancer