Cancer Vaccines and Adjuvants
Two broad types of cancer vaccines exist: preventive cancer vaccines, which target infectious agents causing cancer development, and therapeutic vaccines, which treat an existing cancer by strengthening the body’s natural defense. Like traditional vaccines, preventive cancer vaccines are based on antigens from infectious agents (e.g., virus) that are recognized by the immune system. Therapeutic vaccines treat developed cancers, which the immune system doesn’t often recognize as foreign.
Several factors make it difficult for the immune system to target growing cancer cells. The first is that cancer cells carry normal self antigens as well as specific cancer-associated antigens and these antigens can be lost following genetic changes. Moreover, cancer cells produce messages that suppress anti-cancer immune responses by killer T cells and B cells. Therefore, even when the immune system recognizes cancer cells, such cells can escape and continue to grow. Developing an effective therapeutic cancer vaccine has proven more difficult than producing preventive vaccines. Such vaccines need to stimulate specific immune responses against the correct target and the response must be powerful enough to overcome the barriers cancer cells use to protect themselves against T and B cells.
Generally speaking, targets expressed on cancer cells are poorly immunogenic, meaning they don’t strongly stimulate the immune system. Therefore, vaccines with these targets often require potent immunological adjuvants, which are non-specific agents that stimulate or tune-up the body’s immune defense. Cancer vaccine adjuvants come from many sources, including microbes, biological products derived from non-microbial organisms, non-biological substances or cytokines (substances produced by leukocytes to regulate the immune response). Many of these activate relevant antigen presenting cells, such as dendritic cells and macrophages and promote effective uptake, processing and presentation of antigens to T cells.
There are currently three categories of cancer vaccines in development or clinical trials.
Tumor Antigen-Based Vaccines
These vaccines introduce cancer antigens in the body to prime the immune system. Such vaccines often require adjuvants to further strengthen the immune response. Synthetic tumor antigens or DNA/RNA sequences (naked or in vectors) can be injected. Both strategies allow the immune system to recognize tumor-associated antigens and destroy tumor cells with that antigen. With recent advances in protein chemistry and genomics, many potential cancer-associated antigens have been identified, several of which are being used currently to create experimental cancer vaccines. Some of these antigens are unique to specific cancers; others are found on or in many types of cancer cells. Carbohydrate cancer antigens are an attractive option as they are found in many cancers at an early stage and are absent from normal cells.
The second strategy uses antibodies for cancer therapy. One approach includes anti-idiotype antibodies, which are antibodies directed against antibodies. Antibodies against co-stimulatory T cell molecules is another strategy. In both cases, antibodies are given to directly or indirectly activate T cells. Adjuvants are usually not required with these vaccines as the antibodies can induce a long-lasting immune response.
While the above vaccines introduce molecules into patients to generate anti-tumor immune responses, the third strategy involves administering entire cells into a patient. Through this method inactivated tumor cells with or without adjuvants are introduced, stimulating the immune system to recognize an existing tumor. The advantage of this method is that key tumor antigens, most of which are unknown, don’t need to be identified. Dendritic cells, which take up antigens from tumor cells and then present these antigens to lymphocytes to prime the immune system are also used in cancer vaccine therapies. In this case a patient’s dendritic cells are collected, loaded with tumor antigens from the patient’s own tumor and then re-introduced into circulation, stimulating the immune system. In combination with adjuvants, this strategy has proven to be effective with certain cancers. Another strategy involves injecting T cells or Natural Killer cells which provoke a graft-versus-tumor reaction and induces destruction of the tumor.
Several vaccines using the strategies above are currently in clinical trials to treat various cancers. While the development of cancer vaccines has been challenging, its future appears promising. By better understanding how cancer cells evade the immune system and by developing new adjuvants to boost the immune system cancer will no longer be invincible as it is now regarded.