Therapeutic vaccines for cancer

ALSO KNOWN AS: Biological therapy, immunotherapy

DEFINITION: Therapeutic vaccines treat cancer by stimulating the body’s natural immune system. Therapeutic vaccines contain the whole cancer cell, parts of cells, or components of the body’s immune system.

Cancers treated: By 2024, the US Food and Drug Administration (FDA) had approved three cancer vaccines. Sipuleucel-T (trade name Provenge) is used to treat advanced stages of prostate cancer. Bacillus Calmette-Guerin is approved for the treatment of high-risk, non-muscle-invasive bladder cancer. Talimogene laherparepvec has been approved for the treatment of melanoma. Vaccines have been shown to extend a patient's life, but there currently is not an approved vaccine on the market that cures cancer. Many cancer vaccines are still in clinical trials.

Subclasses of this group: Whole cell vaccines, heat shock proteins, antigen/adjuvant vaccines, dendritic cell vaccines, anti-idiotype vaccines, DNA vaccines

Delivery routes:Cancer vaccines may be delivered by scarification (scratch), subcutaneous or injection, or intranasally. The delivery route depends on the type of vaccine and cancer.

How these drugs work: The immune system is very complex and interconnected. It comprises various white blood cells (lymphocytes) and cytokines. The immune system is stimulated when it identifies foreign molecules known as antigens. The immune response can be either humoral (body fluids) or cellular. Phagocytes (macrophages and dendritic cells) engulf and digest cells and particles in the cellular process. The resultant fragments are attached to a molecule known as the major histocompatibility complex (MHC) and are presented on the cell surface. They are, therefore, known as antigen-presenting cells (APCs). If helper T cells recognize the fragments as antigens, they can either activate B cells to produce antibodies or activate cytotoxic T cells to kill the foreign invader or cancer cell directly. Another process involves natural killer (NK) cells. These cells are activated to destroy cancer cells when they recognize abnormalities on the surfaces of cells. Cytokines are soluble proteins secreted by activated immune cells. They facilitate communication and function among immune system components and enhance the immune response.

Therapeutic vaccines are used to treat existing cancers, in contrast to the traditional role of vaccines to prevent infectious diseases. The immune response is precise, so cancer vaccines have been developed to selectively destroy cancer cells without harming normal cells. Unfortunately, the field has been fraught with disappointments over the last century. A fundamental problem lies with the fact that cancer cells are derived from normal cells. Success depends on the immune system recognizing minimal molecular differences between normal and cancer cells. Although the immune system responds naturally to cancer cells, this response is often weak, and the cancer may be tolerated.

Cancer cells develop many methods to evade the immune system. They can hide their identity by repressing the display of their antigens. They can alter their metabolism to resist attacks by the immune system. They can secrete cytokines that kill lymphocytes. Cancer cells can actively suppress dendritic and T cells' activation and function. Cancer cells can actively suppress the activation and function of dendritic cells and T cells.

A variety of therapeutic vaccines have been developed. A key goal of the vaccines is to enhance the immune system’s response to cancer antigens. Preparations include whole-cell vaccines, heat shock proteins, antigen/adjuvant vaccines, dendritic cell vaccines, anti-idiotype vaccines, and DNA vaccines.

Whole-cell vaccines are prepared from the patient’s whole cancer cells. They do not require the identification of antigens, but they presumably contain the full array of cancer antigens. Unfortunately, early whole-cell vaccines were not very effective. Researchers discovered that T cells are activated only when a second co-stimulatory molecule is present. Whole-cell vaccines are genetically modified to secrete cytokines or express co-stimulatory molecules.

Heat shock proteins are found in most cells and serve to repair protein structure. They are often found in excess in cancer cells. Vaccines are prepared by purifying heat shock proteins from tumor tissue removed from the patient and linking these to tumor antigens. Administration of the vaccine results in uptake and processing by APCs and a strong T-cell response.

Antigen/adjuvant vaccines are prepared by combining a known cancer antigen with a chemical called an adjuvant, which enhances the antigen's effect.

Dendritic cell vaccines have been found to be very effective. To prepare the vaccines, dendritic cells are removed from the patient, exposed to the patient’s cancer antigens in the laboratory, and grown in culture. When the resultant vaccine is injected into the patient, the T cells in the immune system are stimulated to attack the tumor cells.

Anti-idiotype vaccines have been developed for use against cancers that poorly present antigens. Antibodies that are produced in response to an antigen have unique antigen regions called idiotypes. The body can produce antibodies to these idiotypes called anti-idiotypes. Anti-idiotype vaccines can be prepared in the laboratory, often using synthetic monoclonal antibodies. Since these anti-idiotype vaccines appear like the tumor antigen, they stimulate a stronger immune response.

DNA vaccines are based on genes that code for antigen proteins. When these vaccines are administered, they are taken up by APCs. The vaccines are delivered to the APCs using vectors, such as modified viruses, bacteria, or synthetic polymers. Antigen protein is produced and presented to the T cells within the APCs. This method provides a continuous supply of antigens to maintain the immune response.

Side effects: The primary concern with therapeutic vaccines is the development of autoimmune responses, although this seldom occurs. Some patients may experience a skin reaction or mild flulike symptoms.

Bibliography

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