Diseases Preventable By Vaccines

Definition

A cancer vaccine is a method of treating the disease involving administration of one or more substances characteristic of the cancer, called antigens, often in combination with factors that boost immune function. This induces the patient's immune system to attack and eliminate the cancerous cells.

Purpose

Unlike traditional vaccines for infectious diseases, at this time cancer vaccines are not given to prevent the initial development of cancer. Instead, cancer vaccines are a method of treating cancer that has already occurred and are given to patients already diagnosed with cancer.

As a cancer treatment method, the ultimate goal of most cancer vaccines is the elimination of tumor or cancerous cells from the body. Other vaccines are given after the use of more traditional treatments, such as chemotherapy, radiation, or surgery, with the aim of suppressing the recurrence of the cancer.

Precautions

No vaccine has yet been approved by the Food and Drug Administration (FDA) for the treatment of cancer. Accordingly, vaccines are not standard treatments and other more traditional treatments should be investigated first. Vaccines are available only through participation in clinical trials. Each trial has its own criteria that can limit who can participate. However, many cancers have a current trial for one or more types of vaccines. The American Society for Gene Therapy states that as of late 2000, vaccines were the most common approach to gene therapy being studied by researchers.

Most vaccine trials test the response of the disease with and without the vaccine or the effect of substances added to the vaccine, called adjuvants. Such trials usually only accept patients that have already tried the standard treatment methods. Others test a standard treatment method with and without the addition of the vaccine. A very few compare the standard treatment to the vaccine.

Looking at cancer vaccines overall, this treatment method has been more successful eliminating very small tumors rather than the getting rid of a large tumor load. So if the size of the tumor is significant, a more realistic goal is to shrink the tumor and reduce its effect on the patient's body, rather than total elimination of the cancer.

The complexity of the human immune system has made it very difficult to develop an effective vaccine. Tumors have strategies to evade detection by the immune system. Most notably, they mimic the outward appearance and antigens of the body's own cells. The immune system's built-in lack of response against "self" allows the tumor to escape notice by the body. Now fully aware of this phenomenon, researchers are working to develop methods of circumventing this problem to develop a highly effective vaccine system.

Description

There are three general types of cancer vaccines, those that use whole tumor cells, those that use only one or more substances derived from the tumors, or those that administer primed cells from the patient's immune system.

Whole cell vaccines

Whole cell vaccines are autologous when they contain only inactivated tumor cells from the patient's own tumors. The cells have been isolated from the tumor and made to grow in the laboratory, a process known as creating a cell line. Allogeneic whole cell vaccines are made from inactivated tumor cells isolated from one or more other people. The main advantage to autologous vaccines is the direct relation between the vaccine and the tumor target. However, because of the screening of self antigens away from a body's own immune system, immune response to tumor antigens in autologous whole cells vaccines can be low.

Allogeneic vaccines avoid some of the problems of autologous vaccines. First, cell lines do not have to be created for each patient, a labor-intensive process that can have highly variable results. Second, the same vaccine can be given to all patients, making the response to the vaccine more predictable. Third, a use of a pool of tumor cells can increase the possibility of having the full repertoire of the tumor antigens in the vaccine. This helps to overcome the ability of tumor cells to escape notice by the immune system. Finally, by using well-characterized cell lines, it is much easier for the researcher to add genetic modifications that increase the immune system's response to the cells.

Isolated antigen vaccines

There are many kinds of vaccines that deliver only a portion of the tumor cell that will elicit an immune response, called an antigen. Some antigens are unique to a cancer type, some are unique to an individual tumor, while a very few are found in more than one cancer type. For example, vaccines against telomerase and human chorionic gonadotripin (hCG), two proteins produced by many cancers, have been developed, raising hopes for the development of a universal cancer vaccine.

The most common kind of antigen used in cancer vaccines is a protein or a part of a protein. The protein can actually be isolated from the tumor cells, or more commonly, produced in large quantity using genetic engineering techniques. When a part of a protein is used, experimental efforts generally preceded the vaccine production to determine what parts of the protein were often the target of immune responses. Parts of proteins that elicit immune responses are called epitopes.

Antigens do not necessarily have to be proteins. Immune responses are also mounted against the carbohydrate (sugar) molecules present on the surface of the proteins. Tumor proteins can have unusual carbohydrate structures that set them apart from cells from normal tissue. Carbohydrates are also found in abundant numbers on the surface of the tumor cells. Accordingly, researchers have developed cancer vaccines that combine the tumor-characteristic carbohydrates anchored on protein bases. These vaccines are being tested for their ability to reduce the recurrence of prostate cancer.

Vaccines can also contain the naked genetic material encoding the protein (either deoxyribose nucleic acid, DNA, or ribose nucleic acid, RNA). After the genetic material gains entry to the cell, the cellular machinery uses it to produce the antigen and an immune response is mounted against it. Animal studies have found that these types of vaccines are very dependent on the particular antigen and the mode of administration of the vaccine. A unique method of delivery used with DNA or RNA vaccines is the coating of tiny gold beads with the genetic material and shooting the beads into the skin.

Genetically engineered viruses can also be used to bring the DNA or RNA into the cell. When used in this way the viruses are called viral vectors. One example of a viral vector currently being used as a cancer vaccine is one based on the adenovirus. When viruses are used as vectors they have been altered to no longer cause disease, but they do retain the ability to infect human cells. Instead of making new viruses, the infected cells make the desired antigen, and the body will respond against it. Viral vectors can also carry the genetic instructions for factors, called cytokines, which boost the immune system's response to the antigen.

Antigen-presenting cell (APC) vaccines

Vaccines can also be made that contain cells from the patient's own immune system, in particular APCs (antigen-presenting cells). These cells play a central role in the development of an immune response against a particular antigen. Specifically, APCs ingest the antigen and present them to the T cells, a type of immune cells responsible for targeting and killing cells seen as foreign to the body. If T cells are exposed to the antigen by an APC, as opposed to seeing the antigen on the cell itself, they are more strongly activated. That is, more T cells that specifically attack that antigen are produced and the immune response against the foreign cell is stronger.

Dendritic cells are a type of APC that is most effective in activating T cells. For this reason, they are often the kind of cells used in APC vaccines. Unfortunately, the number of dendritic cells circulating in the blood at any one time is relatively low. However, new techniques have been developed that allow that small number of dendritic cells to be isolated and then stimulated outside the body to result in a usable number. During stimulation, the dendritic cells are exposed to the tumor antigen, a process known as priming. Thus, when injected into the body, the dendritic cells are primed to recruit large numbers of T cells specific against the tumor antigen.

Cyokines and adjuvants

Because of the ability of tumor cells to escape detection by the immune system, an important component of many cancer vaccines is the addition of biological factors or chemical adjuvants to help boost immune response. One type of adjuvant is a cytokine, a factor normally produced by cells of the immune system to help recruit cells to the site of the foreign cells or help T cells function. Some examples of cytokines used in vaccines are granulocyte/macrophage colony stimulating factor (GM-CSF, or sargramostim), the interleukins (especially IL-2), the interferons (INFs), and tumor necrosis factor alpha (TNF-).

Adjuvants are chemical additions to vaccines that help boost the response to the contained cells or antigens. Adjuvants are derived from a variety of sources and can be isolated from animals, plants, or are synthetic chemical compounds. Several adjuvants in use with cancer vaccines are keyhole lympocianin (KLH, derived from shell-dwelling sea animals), incomplete Freud's adjuvant (IFA, mineral oil and an emulsifying agent), and QS-21 (a chemical derived from the soapbark tree).

Administration

The particular administration method and schedule will vary from clinical trial to clinical trial. Administration methods can include intradural (injection within the skin), subcutaneous (injection below the skin), injection into the lymph nodes, or intravenous (injection into the veins). Typically, vaccines are administered as a series of several doses (initial challenge and boosters). Many clinical trials utilize various administration methods and timing strategies in order to try to determine the best means of inducing an anti-tumor immune response.

Preparation

Before enrolling in a clinical trial, patients should discuss the potential benefits and risks with their doctor. Clinical trials can be located by contacting the research institutes directly or by searching the Internet. A particularly good site for getting information about clinical trials for cancer treatment is run by the National Cancer Institute (<http://www.clincialtrials.gov>).

Aftercare

One of the most striking advantages of vaccines compared to other cancer treatments is the relatively low incidence of side effects. Particularly if IFN is used as an immunoadjuvant, patients sometimes experience flu-like symptoms. However, other than some soreness at the site of injection, vaccine patients generally have no adverse reactions to this kind of treatment.

Risks

The greatest risk with cancer vaccines is that there will be no immune response and the treatment will be ineffective. Although serious adverse reactions to the antigens, such as the attack of healthy cells, are theoretically possible, these fears have not materialized. Other than some mild adverse reactions, such as fever and redness of the skin at the injection site, vaccine treatment appears relatively low-risk in the traditional sense.

Normal results

Based on a review of published clinical trials as of 2000, normal results for this treatment is, unfortunately, little or no effect. Although a response by the immunized patient's T cells against the tumor is often documented by testing, the effect on disease is generally marginal. These results could be at least partially due to the selection process for patients in the trials, who are often suffering from late-stage cancers.

Abnormal results

For each trial, there are a small percentage of patients who have complete, partial, or mixed response to the vaccine. Others show a stabilization of the disease where deterioration of condition would be expected. As traditional treatments were often unsuccessful with these patients, these results are significant. However, the very low rate of success underscores the complexity of the human immune system, the number of variables in the vaccine method, and the amount of research that will need to be done to develop an effective vaccine treatment for this disease.

See Also Monoclonal antibodies; Immunologic therapy

Resources

BOOKS

Restifo, Nicholas, et al. "Therapeutic Cancer Vaccines." InCancer Principles & Practice of Oncology, edited by DeVita, Vincent T., et al. Philadelphia: LippincottWilliams & Wilkins, 2001, pp. 3195-217.

PERIODICALS

Bocchia, Monica, et al. "Antitumor Vaccination: Where WeStand." Haematologica 85 (November 2000): 1172-206.

Monzavi-Karbassi, B., and T. Kieber-Emmons. "Current concepts in cancer vaccine strategies." Biotechniques 30 (January 2001): 170.

OTHER

"First Potential Universal Cancer Vaccine Shows Promise InLab." Science Daily Magazine. 30 August 2000. 12 April 2001. 28 June 2001 <http://www.sciencedaily.com/print/2000/08/000830073711.htm>.

"Treating Cancer with Vaccine Therapy." Cancer Trials. July 20, 1999. 12 April 2001. 28 June 2001.<http://cancertrials.nci.nih.gov/news/features/vaccine/index.html>.

Michelle Johnson, M.S., J.D.

Adjuvant

—A substance added to a vaccine to increase the immune system's response to the vaccine contents.

Allogeneic

—A type of vaccine made up of tumor cells derived from persons other than the patient.

Antigen

—A substance characteristic of a tumor that evokes an immune response.

Antigen presenting cell

—A cell of the immune system that ingests antigens and exposes them to cells of the immune system in a way that activates the cells to seek out and destroy any other cells displaying that antigen.

Autologous

—A type of vaccine made up of tumor cells from the patient's own tumor.

Cytokine

—A substance made by cells of the immune system that increases the response to a foreign substance.

Dendritic cell

—A special type of antigen-presenting cell that is effective in stimulating T cells.

Epitope

—A portion of a protein or other molecule that is the specific target of an immune response.

QUESTIONS TO ASK THE DOCTOR

  • Have all the standard treatment methods for my cancer been tried?
  • Is there a vaccine in clinical trials for my kind of cancer?
  • Do I fulfill the requirements necessary for the clinical trial for this vaccine?
  • Has this vaccine been tried on human patients before?
  • If so, what were the results?