How cancer vaccines work

A vaccine fights infection by enabling the body’s natural immune system to better recognize the pathogen. Immune cells called T cells and B cells look for specific antigens, usually small pieces of cells or viruses that the immune system recognizes as foreign. T cells identify and kill cells or viruses that contain the antigen, and B cells produce antibodies that attach to the antigen and kill the cell or virus by indirect means. T cells and B cells are lymphocytes – white blood cells.  Each T and B cell recognizes a different antigen, and when it finds its target, it makes many copies of itself. This way, the body targets the invasion by reproducing the cells that go after the specific substance that has already been identified as foreign.

A vaccine just gives the immune system a head start in this very same process. A vaccine for smallpox contains smallpox viruses that are disabled so that they cannot infect the human body. When the viral particles enter the cell, the T cells and B cells that recognize the virus replicate themselves, so the immune system already has plenty of cells looking for smallpox viruses if NS when the real viruses show up in the bloodstream. The viruses are then attacked immediately upon entrance into the body and never get the chance to infect the person. The vaccine triggers the natural immune response so that it is underway before the pathogen even enters the body.

Cancer vaccines also stimulate an immune response, but direct it towards cancer cells or viruses that cause cancer. An effective cancer vaccine elicits both humoral (antibody) responses and cellular (antigen-specific T-cell) responses. For cancer caused by viruses, the vaccine mechanism is no different from any other disease; the vaccine simply consists of disabled viruses that cause cancer, such as human papillomavirus, instead of disabled smallpox viruses. The FDA has approved a vaccine against two strains of HPV that cause nearly 70 percent of all cervical cancers.

Most tumors, however, are not caused by viruses, so the vaccination strategy must be broadened to deal with a wider variety of cancers. Because of their mutations, the surfaces of the tumor cells are slightly different from the surfaces of the normal cells; the parts of the surface that are different can be used as antigens to activate the immune system. However, because they are human cells, the surfaces of tumor cells are less likely to be recognized as foreign by the immune system. Vaccines are designed to make those cells more identifiable as foreign.  Most cancer vaccines target  tumor-associated or tumor-specific antigens (TAAs or TSAs).  If  they work correctly, they destroy malignant cells that overexpress the antigens and produce a long-term therapeutic response from the body’s immunologic memory.

To complicate matters further, cancer cells sometimes shed molecules that inhibit immune responses, so considerably more creativity is required to trigger an immune response against them.  Researchers have developed a variety of strategies to address these issues. The first step is to identify the molecules that are unique or almost unique to cancer cells and direct the immune system against them by using them as vaccines. This will allow the T cells to attack the cancer cells and the B cells to make antibodies that inhibit the growth of the cells.

In order to strengthen the immune response to the vaccine the antigen can be modified to make it look more foreign by exaggerating the differences between it and the corresponding molecule in a normal cell. As long as the antigen still resembles the tumor antigen enough, the T and B cells that recognize it will also recognize the tumor cells. The gene that produces the antigen may also be put into a harmless virus, which inserts the gene into the DNA of either cancer or normal cells. Once the extra gene is inserted, these cells will produce far more of the antigen, and therefore cause a stronger immune response. Either the virus with the gene for the antigen inserted or a cell that was infected with the virus and is producing many copies of the antigen may be used as vaccines.

A second strategy involves taking advantage of another type of cell called an antigen presenting cell (APC), which continually eats various pieces of matter and displays parts of them on its surface. The T cells and B cells become activated when they come across an APC with the antigen they recognize on its surface. Injecting an APC that is displays tumor antigens can be very useful in stimulating an immune response, as it will activate the correct T and B cells. In order to get the APC to present tumor antigens, the APC’s may be infected with a virus that inserts the gene that codes for the tumor antigen into the DNA of the APC, or the APC’s may be fed tumor antigens or the DNA or RNA that codes for the antigen.

research into cancer treatment methodsAntibodies that have binding sites that look like the tumor antigen, called anti-idiotype antibodies, can also be used to stimulate B cells to make antibodies against them. Because the B cell makes antibodies against the part of the anti-idiotype antibody that looks like the tumor antigen, the B cell’s antibodies also function to disable the tumor cells.

The tumor antigens used to make the vaccines can be from either the patient the vaccine will be used on or another patient. When they are from the patient they will be used on, they are called autologous vaccines. These antigens in these vaccines are more specific to the patient, but these vaccines are, of course, more expensive to produce. Vaccines made from another patient with the same type of tumor are called allogenic vaccines and are more cheaply given to many people.