CancerQuest | Non-Specific and Cytokine Therapies

This group of tumor vaccine strategies stimulates an enduring immune response in the body, but does not directly target tumor-specific T cells. These vaccines and vaccine supplements increase the general immune response, and this includes the antitumor response.

The two broad categories of this strategy are BCG and cytokines:

BCG-One of the earliest and, to date, most successful tumor vaccine strategies,dating from the early 1970s, is the use of a bacterium-bacillus Calmette-Guérin (BCG). BCG was originally developed as a vaccine against the bacterial infection that causes tuberculosis, but has been found to work in treating bladder cancer. It is often administered directly to the bladder via a catheter. While the exact mechanism by which BCG works is not clear, it is believed to increase inflammation. While this sounds like it may be counter-productive, Inflammation increases the blood flow to the tumor containing areaand brings in an increased number of antigen presenting cells (APCs) and T cells. So far, BCG has demonstrated the best response in the treatment of bladder cancer.
Cytokines- Cytokines are molecules, usually small proteins, that are naturally produced by immune cells. Immune system cells use cytokines to send messages to each other. The goal of administering cytokines is to attract additional immune cells to the site of the tumor and to stimulate the reproduction of immune cells.

The proteins that have been investigated include:

Interleukins-There are a number of proteins that are produced by white blood cells (leukocytes; leuko=white, cyte=cell). Among them are the interleukins (IL). (inter=between, leuko=referring to white blood cells). Interleukins are used for cell to cell communication and can act to stimulate cell division of the target cells. Those used in cancer treatment include IL-2 and IL-12. Both act as essential growth factors for T cells.
Granulocyte-Macrophage Colony-Stimulating Factor(GM-CSF): This protein is produced by a variety of cells types and has numerous affects on cells of the immune system. Amont the functions attributed to GM-CSF: attraction of dendritic cells, the key APCs in the body, and stimulation of dendritic cell production and activation.
Interferons (IFN-gamma and IFN-alpha): stimulate the activation of cytotoxic T cells and promote inflammation. In other roles, the interferons are involved in the defense against viral infection.

The approaches described above stimulate the immune system in general (tumor-specific T cells are not targeted directly). This general stimulation of the immune response has in fact been shown to generate an anti-tumor response in patients. Although administration of these cytokines alone has shown promising results in patients, the high doses used also had toxic side effects. Researchers and physicians are using low doses of cytokines in combination with some of the other tumor vaccines strategies that have been discussed, such as gene-modified tumor cell vaccines and dendritic cell vaccines. When cytokines are injected as supplements to another vaccine strategy, they are called an adjuvant therapy because they act to increase the effectiveness of the primary vaccine being used. ⁽¹⁾