Related Pages What Is a Clinical Trial? A basic description of the reason for, and the kinds of, clinical trials. Cancer Vaccines Cancer vaccines are intended either to treat existing cancers (therapeutic vaccines) or to prevent the development of cancer (prophylactic vaccines). Fact Sheet 7.56

The Immune System and Cancer
Making Cancer Treatment Vaccines
Added Ingredients

The Immune System and Cancer

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 “tolerate” 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 “tumor antigens” as vaccines.
• Intervene to make tumor antigens more visible to the immune system. This can be done in several ways:
  • 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.
  • 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.
  • Put genes for other molecules that normally help stimulate the immune system into a viral vector along with a tumor antigen gene.
• Use “primed” dendritic cells or other APCs as a vaccine. There are three ways to prime a dendritic cell.
  • APCs can be fed tumor antigens in the laboratory and then injected into a patient. The injected cells are primed to activate T cells.
  • Alternatively, APCs can be infected with a viral vector that contains the gene for a tumor antigen.
  • 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.
• 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.

Making Cancer Treatment Vaccines

Cancer treatment vaccines can be made using a patient’s own tumor antigens or cells, or someone else’s. Most tumors of a given type share many antigens. When a patient’s own tumor antigens or cells are used, the vaccine is called an autologous vaccine. When someone else’s tumor antigens or cells are used, the vaccine is called an allogeneic vaccine.

Added Ingredients

Cancer vaccines often have added ingredients, called adjuvants, that help boost the immune response. These substances may also be given separately to increase a vaccine’s effectiveness. Many different kinds of substances have been used as adjuvants, including cytokines, proteins, bacteria, viruses, and certain chemicals.

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