Posted on April 25, 2011 Comments (4)
A reader commented on a previous post (MIT Engineers Design New Type of Nanoparticle for Vacines) asking about how vaccines can fight cancer. Preventative vaccines can build up immune response to viruses which cause cancer. So the vaccine actually works against the virus which prevents the virus from causing cancer.
The U.S. Food and Drug Administration (FDA) has approved two vaccines, Gardasil® and Cervarix®, that protect against infection by the two types of human papillomavirus (HPV) – types 16 and 18 – that cause approximately 70% of all cases of cervical cancer worldwide. At least 17 other types of HPV are responsible for the remaining 30% of cervical cancer cases. HPV types 16 and/or 18 also cause some vaginal, vulvar, anal, penile, and oropharyngeal cancers.
Many scientists believe that microbes cause or contribute to between 15% and 25% of all cancers diagnosed worldwide each year, with the percentages being lower in developed than developing countries.
Vaccines can also help stimulate the immune system to fight cancers.
B cells make antibodies, which are large secreted proteins that bind to, inactivate, and help destroy foreign invaders or abnormal cells. Most preventive vaccines, including those aimed at hepatitis B virus (HBV) and human papillomavirus (HPV), stimulate the production of antibodies that bind to specific, targeted microbes and block their ability to cause infection. Cytotoxic T cells, which are also known as killer T cells, kill infected or abnormal cells by releasing toxic chemicals or by prompting the cells to self-destruct (a process known as apoptosis).
Other types of lymphocytes and leukocytes play supporting roles to ensure that B cells and killer T cells do their jobs effectively. These supporting cells include helper T cells and dendritic cells, which help activate killer T cells and enable them to recognize specific threats.
Cancer treatment vaccines are designed to work by activating B cells and killer T cells and directing them to recognize and act against specific types of cancer. They do this by introducing one or more molecules known as antigens into the body, usually by injection. An antigen is a substance that stimulates a specific immune response. An antigen can be a protein or another type of molecule found on the surface of or inside a cell.
Microbes are recognized by the immune system as a potential threat that should be destroyed because they carry foreign or “non-self” antigens. In contrast, 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.
Cancer cells can carry both self antigens and cancer-associated antigens. The cancer-associated antigens mark the cancer cells as abnormal, or foreign, and can cause B cells and killer T cells to mount an attack against them.
Cancer cells may also make much larger amounts of certain self antigens than normal cells. Because of their high abundance, these self antigens may be viewed by the immune system as being foreign and, therefore, may trigger an immune response against the cancer cells.
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.
The International Agency for Research on Cancer (IARC) has classified several microbes as carcinogenic (causing or contributing to the development of cancer in people), including HPV and HBV. These infectious agents – bacteria, viruses, and parasites – and the cancer types with which they are most strongly associated are listed in the table below.
|Infectious Agents||Type of
|hepatitis B virus (HBV)||virus||hepatocellular carcinoma (a type of liver cancer)|
|hepatitis C virus (HCV)||virus||hepatocellular carcinoma (a type of liver cancer)|
|human papillomavirus (HPV) types 16 and 18, as well as other HPV types||virus||cervical cancer; vaginal cancer; vulvar cancer; oropharyngeal cancer (cancers of the base of the tongue, tonsils, or upper throat); anal cancer; penile cancer|
|Epstein-Barr virus||virus||Burkitt lymphoma; non-Hodgkin lymphoma; Hodgkin lymphoma; nasopharyngeal carcinoma (cancer of the upper part of the throat behind the nose)|
|human T-cell lymphotropic virus 1 (HTLV1)||virus||acute T-cell leukemia|
|Helicobacter pylori||bacterium||stomach cancer|
|schistosomes (Schistosoma hematobium)||parasite||bladder cancer|
|liver flukes (Opisthorchis viverrini)||parasite||cholangiocarcinoma (a type of liver cancer)|
Cancer treatment vaccines are designed to treat cancers that have already developed. They are intended to delay or stop cancer cell growth; to cause tumor shrinkage; to prevent cancer from coming back; or to eliminate cancer cells that have not been killed by other forms of treatment.
Several factors may make it difficult for the immune system to target growing cancers for destruction. Most important, cancer cells carry normal self antigens in addition to specific cancer-associated antigens. Furthermore, cancer cells sometimes undergo genetic changes that may lead to the loss of cancer-associated antigens. Finally, cancer cells can produce chemical messages that suppress 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.
Producing effective treatment vaccines has proven much more difficult and challenging than developing cancer preventive vaccines. Recent advances in understanding how cancer cells escape recognition and attack by the immune system are now giving researchers the knowledge required to design cancer treatment vaccines.
In April 2010, the FDA approved the first cancer treatment vaccine. This vaccine, sipuleucel-T (Provenge®, manufactured by Dendreon), 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 present on most prostate cancers. In a clinical trial, 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 under development, sipuleucel-T is customized to each patient. The vaccine is created by isolating immune system cells called antigen-presenting cells (APCs) from a patient’s blood through a procedure called leukapheresis.
APC cells cultured with PAP-GM-CSF constitute the active component of sipuleucel-T. Each patient’s cells are returned to the patient’s treating physician and infused into the patient. Patients receive three treatments, usually 2 weeks apart, with each round of treatment requiring the same manufacturing process.