A well-defined branch of vaccine from preventative vaccines, therapeutic vaccines are designed to be given to patients who have already acquired an illness capable of avoiding the immune response. By introducing disease-specific stimulatory substances to the immune system in specific techniques, therapeutic vaccines endeavor to activate the immune system selectively against the disease, and improve the patient’s prospects for health. For many illnesses which are intractable to standard treatment, such as hepatitis, tuberculosis or malaria, vaccines that can bring about an aggressive, precise response offer an attractive alternative.
Technologies used in therapeutic vaccines are still developing. Critical components like disease-specific immunogenicity factors, antigen source, the role of co-stimulators and adjuvants, and vaccine delivery are still in research for many conditions. Each patients immune systems responses are highly individualized, makeing patient variability a focal point of vaccine design. While autologous vaccines have the advantage of being specific for each patient’s disease, they are expensive and labor intensive to create. The idea behind allogeneic vaccines is that they would work for every patient with the same disease.
(Vaccines can be made using a patients own antigens or cells, or someone elses. Most tumors of a given type share many antigens. When a patients own tumor antigens or cells are used, the vaccine is called an autologous vaccine. When someone elses tumor antigens or cells are used, the vaccine is called an allogeneic vaccine.)
Researchers used to think that the immune system prevented cancer from growing and spreading by constantly looking to see if cancer cells are present and killing them once they are found. It was thought that the growth and spread of cancer resulted from a breakdown of the immune system. In a broken-down immune system, effective anti-cancer immune responses could not occur.
However, this theory of immune system control over cancer growth has now been shown to be only partially correct. Researchers now know that strong immune responses against cancer cells are hard to generate, and they are studying ways to strengthen the ability of the immune system to fight cancer.
Part of the problem is that the immune system has the job of knowing the difference between normal cells and cancer cells. To keep us healthy, the immune system must be able to ignore or Ã¢â‚¬Å“tolerateÃ¢â‚¬Â normal cells and recognize and attack abnormal ones.
To the immune system, cancer cells differ from normal cells in very small, subtle ways. Therefore, the immune system largely tolerates cancer cells rather than attacking them. Although tolerance is essential to keep the immune system from attacking normal cells, tolerance of cancer cells is a problem. Therapeutic cancer vaccines must not only provoke an immune response but stimulate the immune system strongly enough to overcome its usual tolerance of cancer cells.
Another reason cancer cells may not stimulate a strong immune response is that they have developed ways to evade the immune system. Scientists now understand some of the ways in which cancer cells do this. For example, they may shed certain types of molecules that inhibit the ability of the body to attack cancer cells. As a result, cancers become less “visible” to the immune system.
Researchers are now using these advances in knowledge in their efforts to design more effective cancer vaccines. They have developed several strategies for stimulating immune responses against cancers, including the following:
* Identify unusual or unique cancer-related molecules that are rarely present on normal cells and use these so-called Ã¢â‚¬Å“tumor antigensÃ¢â‚¬Â as vaccines. * Intervene to make tumor antigens more visible to the immune system. This can be done in several ways: 1. Alter the structure of a tumor antigen slightly (that is, make it look more foreign) and give the altered antigen as a vaccine. One way to alter an antigen is modify the gene needed to make it. This can be done in the laboratory. 2 Put the gene for a tumor antigen into a viral vector (a harmless virus) and use the virus as a vehicle to deliver the gene to cancer cells or to normal cells. Cells infected with the viral vector will make much more tumor antigen than uninfected cancer cells and may be more visible to the immune system. Cells can also be infected with the viral vector in the laboratory and then given to patients as a vaccine. In addition, patients can be infected (that is, vaccinated) with the viral vector as another way to get virus-infected cells inside the body. 3. Put genes for other molecules that normally help stimulate the immune system into a viral vector along with a tumor antigen gene. 4. Use Ã¢â‚¬Å“primedÃ¢â‚¬Â dendritic cells or other APCs as a vaccine. There are three ways to prime a dendritic cell. o APCs can be fed tumor antigens in the laboratory and then injected into a patient. The injected cells are primed to activate T cells. o Alternatively, APCs can be infected with a viral vector that contains the gene for a tumor antigen. o A third way to make primed APCs is to feed the cells DNA or RNA that contains genetic instructions for the antigen. The APCs will then make the tumor antigen and present it on their surface. 5 Use antibodies that have antigen-binding sites that mimic, or look like, a tumor antigen. These antibodies are called anti-idiotype antibodies. They can stimulate B cells to make to make antibodies against tumor antigens. Anti-idiotype antibodies present tumor antigens in a different way to the immune system.
Cancer vaccines often have added ingredients, called adjuvants, that help boost the immune response. These substances may also be given separately to increase a vaccines effectiveness. Many different kinds of substances have been used as adjuvants, including cytokines, proteins, bacteria, viruses, and certain chemicals.