Related Pages What Is a Clinical Trial? 1 A basic description of the reason for, and the kinds of, clinical trials. Cancer Vaccines 2 Cancer vaccines are intended either to treat existing cancers (therapeutic vaccines) or to prevent the development of cancer (prophylactic vaccines). Fact Sheet 7.56

About Vaccines

Immune System Basics

Cancer Vaccine Strategies

When Is a Cancer Vaccine Appropriate?

Present and Future of Cancer Vaccines

Helpful Links

Introduction

For many years, the treatment of cancer was focused primarily on surgery, chemotherapy, and radiation. However, as researchers learn more about how the body fights cancer on its own, therapies are being developed that harness the potential of the body's defense system in this fight, including efforts to prevent some forms of cancer.

The body's defense system - called the immune system - consists of a network of specialized cells and tissues that fight infection and disease. Therapies that use the immune system to fight or prevent cancer are called biological therapies.

Cancer vaccines represent an emerging type of biological therapy that is still mostly experimental. Many clinical trials are underway to test vaccines as potential treatments for a wide variety of cancer types. The U.S. Food and Drug Administration (FDA) has not approved any cancer vaccine as a standard treatment for any type of cancer. This means that cancer-fighting vaccines are only available to those who enroll in clinical trials.

The FDA has, however, approved two vaccines that can help prevent cancer. One of these vaccines prevents infection with the human papillomavirus (HPV), which causes almost all cervical cancers (for more information, see Human Papillomavirus (HPV) Vaccines for Cervical Cancer ³). The other vaccine prevents infection with the hepatitis B virus, which can cause liver cancer. Other vaccines that may prevent or reduce the risk of cancer are also being tested in ongoing clinical trials.

What is a Vaccine?
What are Cancer Vaccines?
Substances Used to Make Vaccines

What Is a Vaccine?

A vaccine is a substance designed to stimulate the immune system to launch an immune response. This response is directed against specific targets, or antigens, that are part of the vaccine. An antigen is any substance that the immune system recognizes as foreign.

The flu vaccine, for example, contains copies of the flu virus that cannot cause the flu. Antigens on the viruses in the vaccine stimulate the immune system to produce cells that can fight the flu virus if it shows up in your nose or throat.

The flu vaccine only works if it is given at least two weeks before exposure to infectious flu virus. The immune system needs those two weeks to produce immune cells that can attack the flu virus.

Because the flu virus changes from year to year, a new flu vaccine is needed every year. Your immune system, however, still protects you against last year's flu type. This type of vaccine is called a preventive vaccine - it stimulates a long-lasting immunity that helps protect you from getting sick for years or even for a lifetime.

What Are Cancer Vaccines?

Cancer vaccines are intended either to treat existing cancer or to prevent the development of cancer. Cancer treatment vaccines are designed to strengthen the body's natural defenses against a cancer that has already developed. These vaccines may stop an existing tumor from growing, stop a tumor from coming back after it has been treated, or eliminate cancer cells not killed by previous treatments.

Cancer preventive vaccines are given to healthy people and are designed to target infectious agents that can cause cancer. The HPV vaccine is an example of a cancer preventive vaccine. It is used to help prevent cervical cancer.

Substances Used to Make Vaccines

Vaccines can be made using specific types of molecules from viruses or cells, including molecules from bacterial cells or human cells. These molecules may contain a single antigen or several different antigens. Carbohydrates (sugars), proteins, and peptides (pieces of proteins) are among the types of molecules that have been used to make vaccines. Molecules of DNA or RNA that contain genetic instructions for one or more antigens can also be used as vaccines (for more information, see Cancer Vaccine Strategies ⁴.)

In addition, whole viruses or cells, or parts of viruses or cells that contain different types of molecules, can be used to make vaccines. The flu vaccine, for example, is made using inactive whole flu viruses. If whole human cells are used as vaccines, they are usually treated with enough radiation to keep them from dividing (growing and multiplying) or enough to kill them.

Back to Top Immune System Basics

Immune System Overview
T Cells, B Cells, and APCs

Immune System Overview

The immune system is made up, in part, of a network of immune cells that form in the bone marrow from a very basic type of cell called a stem cell. Many different types of immune cells can be made from stem cells.

Immune cells circulate in the blood or in a network of channels similar to blood vessels called the lymphatic system. They also congregate in special areas of the lymphatic system called lymph nodes.

Some immune cells have very specific functions. Others have general or non-specific functions. T lymphocytes (T cells) and B lymphocytes (B cells) are examples of specific immune cells.

Each T cell and B cell recognizes and is activated by a single substance. This single substance is called the T cell’s or B cell’s antigen. When a T cell or a B cell recognizes its antigen and is activated, it makes many identical copies of itself. Each copy recognizes the same antigen as the original T cell or B cell.

T Cells, B Cells, and APCs

There are two main types of T cells. Cytotoxic T cells identify and kill cells that contain the antigen they recognize. Helper T cells release chemical messengers called cytokines that recruit other immune cells to the site of attack. Helper T cells also help cytotoxic T cells do their job.

B cells make antibodies. Each B cell makes only one type of antibody, which is directed against its specific antigen. Just as helper T cells help cytotoxic T cells do their job, helper T cells help stimulate B cells to make antibodies. Antibodies specific for an antigen on a cancer cell can attach to the antigen and, by several indirect mechanisms, cause the cancer cell’s death.

The immune system also contains antigen-presenting cells (APCs). APCs sample their surrounding environment, eating whatever they come across, and then they display little bits of what they have eaten on their surface. Macrophages and dendritic cells are examples of APCs.

Macrophages patrol the body, eating dead cells, debris, viruses, and bacteria. Dendritic cells are more stationary, monitoring the surrounding environment from one spot, such as the skin. Lymphocytes (T cells or B cells) that “meet” an APC can look at the APC cell surface and see if their specific antigen is present. If their antigen is present, the lymphocytes become activated.

Both T cells and B cells can be activated in immune responses against cancer treatment or cancer preventive vaccines. With preventive vaccines against infectious agents that cause cancer, the activated B cells may produce antibodies that bind to the agents and interfere with their ability to infect cells. Because the agents must infect cells to make them cancerous, this lowers chances that cancer will occur.

Back to Top Cancer Vaccine Strategies

The Immune System and Cancer
Making Cancer Treatment Vaccines
Added Ingredients

The Immune System and Cancer

Researchers used to think that the immune system prevented cancer from growing and spreading by constantly looking to see if cancer cells are present and killing them once they are found. It was thought that the growth and spread of cancer resulted from a breakdown of the immune system. In a broken-down immune system, effective anti-cancer immune responses could not occur.

However, this theory of immune system control over cancer growth has now been shown to be only partially correct. Researchers now know that strong immune responses against cancer cells are hard to generate, and they are studying ways to strengthen the ability of the immune system to fight cancer.

Part of the problem is that the immune system has the job of knowing the difference between normal cells and cancer cells. To keep us healthy, the immune system must be able to ignore or “tolerate” normal cells and recognize and attack abnormal ones.

To the immune system, cancer cells differ from normal cells in very small, subtle ways. Therefore, the immune system largely tolerates cancer cells rather than attacking them. Although tolerance is essential to keep the immune system from attacking normal cells, tolerance of cancer cells is a problem. Therapeutic cancer vaccines must not only provoke an immune response but stimulate the immune system strongly enough to overcome its usual tolerance of cancer cells.

Another reason cancer cells may not stimulate a strong immune response is that they have developed ways to evade the immune system. Scientists now understand some of the ways in which cancer cells do this. For example, they may shed certain types of molecules that inhibit the ability of the body to attack cancer cells. As a result, cancers become less "visible" to the immune system.

Researchers are now using these advances in knowledge in their efforts to design more effective cancer vaccines. They have developed several strategies for stimulating immune responses against cancers, including the following:

• Identify unusual or unique cancer-related molecules that are rarely present on normal cells and use these so-called “tumor antigens” as vaccines.
• Intervene to make tumor antigens more visible to the immune system. This can be done in several ways:
  • Alter the structure of a tumor antigen slightly (that is, make it look more foreign) and give the altered antigen as a vaccine. One way to alter an antigen is modify the gene needed to make it. This can be done in the laboratory.
  • Put the gene for a tumor antigen into a viral vector (a harmless virus) and use the virus as a vehicle to deliver the gene to cancer cells or to normal cells. Cells infected with the viral vector will make much more tumor antigen than uninfected cancer cells and may be more visible to the immune system. Cells can also be infected with the viral vector in the laboratory and then given to patients as a vaccine. In addition, patients can be infected (that is, vaccinated) with the viral vector as another way to get virus-infected cells inside the body.
  • Put genes for other molecules that normally help stimulate the immune system into a viral vector along with a tumor antigen gene.
• Use “primed” dendritic cells or other APCs as a vaccine. There are three ways to prime a dendritic cell.
  • APCs can be fed tumor antigens in the laboratory and then injected into a patient. The injected cells are primed to activate T cells.
  • Alternatively, APCs can be infected with a viral vector that contains the gene for a tumor antigen.
  • A third way to make primed APCs is to feed the cells DNA or RNA that contains genetic instructions for the antigen. The APCs will then make the tumor antigen and present it on their surface.
• Use antibodies that have antigen-binding sites that mimic, or look like, a tumor antigen. These antibodies are called anti-idiotype antibodies. They can stimulate B cells to make to make antibodies against tumor antigens. Anti-idiotype antibodies present tumor antigens in a different way to the immune system.

Making Cancer Treatment Vaccines

Cancer treatment vaccines can be made using a patient’s own tumor antigens or cells, or someone else’s. Most tumors of a given type share many antigens. When a patient’s own tumor antigens or cells are used, the vaccine is called an autologous vaccine. When someone else’s tumor antigens or cells are used, the vaccine is called an allogeneic vaccine.

Added Ingredients

Cancer vaccines often have added ingredients, called adjuvants, that help boost the immune response. These substances may also be given separately to increase a vaccine’s effectiveness. Many different kinds of substances have been used as adjuvants, including cytokines, proteins, bacteria, viruses, and certain chemicals.

Back to Top When Is a Cancer Vaccine Appropriate?

Only you can make decisions about what treatment you should have. You should always discuss any treatment option thoroughly with your doctor and possibly your loved ones. The following questions and answers may help you to think about whether taking part in a cancer vaccine trial might be an appropriate option for you.

Is a standard treatment available for my cancer?

If a standard treatment exists for your cancer, you should not choose an experimental vaccine therapy over the standard treatment. The FDA has not yet approved any cancer vaccine for use as a standard treatment. A vaccine may be an appropriate addition to standard therapy but not a replacement for it. Currently, many therapeutic cancer vaccines are being used after the patient finishes standard treatment.

Some cancer vaccine trials test a standard treatment with or without the vaccine. A few test the standard therapy against the vaccine. Some cancer vaccine trials test the cancer vaccine against a placebo vaccine or test the cancer vaccine in combination with various adjuvants. In these cases, the patient has already received standard therapy.

Is the main goal of treatment to prevent my cancer from coming back or to shrink existing tumors?

In studies using laboratory animals, cancer vaccines show the most promise at preventing cancer from coming back after the primary tumor has been eliminated by surgery, radiation, or chemotherapy. When the immune system has to detect and fight a smaller number of cancer cells, it is more likely to be successful. In contrast, shrinking existing tumors using vaccine therapy is more difficult. When the immune system is matched against a large number of cancer cells, it is more likely to be overwhelmed and ineffective—an out-numbered army.

It may be appropriate to consider experimental cancer vaccines for advanced cancers once all other therapies have been exhausted, when standard therapy is no longer effective, or in combination with other therapies. For example, in some patients with melanoma and renal cell cancers, treatment with the cytokine called interleukin-2 (IL-2) has caused large tumors to shrink. Many current cancer vaccine clinical trials are testing vaccines in combination with other therapies such as IL-2. It is also possible that newer and more potent vaccine strategies could cause advanced cancers to shrink.

In studies conducted in laboratory animals, cancer vaccines that stimulate the immune system have caused cancers to recede. In humans, however, the situation is more complicated. As discussed in Cancer Vaccine Strategies ⁵, cancers have developed ways of evading the immune system. Researchers now have a better understanding of how cancer cells avoid detection by the immune system, and they have developed new strategies for stimulating a more powerful anticancer immune response.

Therapeutic cancer vaccines have shown promise in early-stage clinical trials against several types of cancer, for example:

• In one early-stage study, 18 of 20 patients who were vaccinated against non-Hodgkin's lymphoma stayed in remission for an average of four years (see the journal abstract). The vaccine used in this study contained a protein specific to each patient’s tumor cells (that is, each patient was given an autologous vaccine) as well as two other substances to help boost the immune response. A large, randomized, phase III trial of this vaccine is now under way. (See Lymphoma Vaccine Enters Large Scale Clinical Trials ⁶.)
• In a phase I/II study (see the journal abstract), three of 33 patients with advanced non-small cell lung cancer had a complete remission of disease and were still alive at least three years after vaccine therapy. To make the vaccine, researchers added the gene for the cytokine granulocyte–macrophage colony stimulating factor (GM-CSF) to each patient's tumor cells - that is, each patient was given an autologous vaccine.
• Another early-stage trial showed that, when administered along with a melanoma peptide vaccine, an antibody that blocks the activity of a key immune-system regulatory molecule caused tumors to shrink in patients with metastatic melanoma. (See Researchers Shut Off Immune Cell Inhibition, Causing Tumor Shrinkage and Autoimmunity in Patients With Metastatic Melanoma ⁷.)

It is important to note that the promise of early-stage clinical trials, which usually enroll only a small number of patients, is not always sustained in larger trials. Early studies of another melanoma vaccine suggested that the vaccine might help prevent melanoma from coming back in patients who were at high risk for recurrence. However, in a subsequent large trial that included 774 patients who were at high risk for melanoma recurrence, high-dose interferon proved superior to the vaccine in preventing melanoma from coming back. (See Interferon Superior to a GMK Vaccine in Preventing Melanoma Relapse ⁸.)

Researchers still have a lot of work to do to demonstrate clearly that cancer treatment vaccines can be effective. It is possible that vaccines will prove more effective when combined with other therapies and that multiple vaccinations may be necessary for a benefit to be seen.

Much work also remains to be done to develop vaccines that can reliably prevent cancers associated with infectious agents. Cervical cancer, for example, is almost always caused by infection with HPV. The FDA has approved a vaccine that prevents infections with two types of HPV that cause nearly 70 percent of all cervical cancers. Researchers must develop new vaccines that are able to prevent infections by all HPV types that can cause this disease.

Ongoing trials seek to find the most promising situations for the use of cancer vaccines and the best approaches for making such vaccines work. Only when rigorous trials provide evidence that a particular cancer vaccine is both safe and effective against a specific type of cancer will the FDA consider approving that vaccine as standard treatment.

The following links will take you to other information on the National Cancer Institute Web site about cancer vaccines:

Glossary Terms

A type of protein made by plasma cells (a type of white blood cell) in response to an antigen (foreign substance). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

A special type of immune cell that is found in tissues, such as the skin, and boosts immune responses by showing antigens on its surface to other cells of the immune system. A dendritic cell is a type of phagocyte and a type of antigen-presenting cell (APC).

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called deoxyribonucleic acid.

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

A substance that helps make more white blood cells, especially granulocytes, macrophages, and cells that become platelets. It is a cytokine that is a type of hematopoietic (blood-forming) agent. Also called granulocyte-macrophage colony-stimulating factor and sargramostim.

The activity of the immune system against foreign substances (antigens).

A biological response modifier (a substance that can improve the body's natural response to infections and other diseases). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -gamma. The body normally produces these substances. They are also made in the laboratory to treat cancer and other diseases.

A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

The smallest particle of a substance that has all of the physical and chemical properties of that substance. Molecules are made up of one or more atoms. If they contain more than one atom, the atoms can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms.

A group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope. The three main types of non-small cell lung cancer are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Non-small cell lung cancer is the most common kind of lung cancer.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

The most common type of kidney cancer. It begins in the lining of the renal tubules in the kidney. The renal tubules filter the blood and produce urine. Also called hypernephroma.

One of the two types of nucleic acids found in all cells. In the cell, RNA is made from DNA (the other type of nucleic acid), and proteins are made from RNA. Also called ribonucleic acid.

A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.

A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors may produce tumor antigens (proteins found on a tumor cell) to stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells.