Cancer Vaccines (Fact Sheet)

Has the FDA approved any cancer treatment vaccines?

In April 2010, the FDA approved the first cancer treatment vaccine. This vaccine, sipuleucel-T (Provenge, manufactured by Dendreon), is approved for use in some men with metastatic prostate cancer. It is designed to stimulate an immune response to prostatic acid phosphatase (PAP), an antigen that is found on most prostate cancer cells. In a clinical trial, sipuleucel-T increased the survival of men with a certain type of metastatic prostate cancer by about 4 months (19).

Unlike some other cancer treatment vaccines under development, sipuleucel-T is customized to each patient. The vaccine is created by isolating immune system cells called antigen-presenting cells (APCs) from a patient’s blood through a procedure called leukapheresis. The APCs are sent to Dendreon, where they are cultured with a protein called PAP-GM-CSF. This protein consists of PAP linked to another protein called granulocyte-macrophage colony-stimulating factor (GM-CSF). The latter protein stimulates the immune system and enhances antigen presentation.

APC cells cultured with PAP-GM-CSF constitute the active component of sipuleucel-T. Each patient’s cells are returned to the patient’s treating physician and infused into the patient. Patients receive three treatments, usually 2 weeks apart, with each round of treatment requiring the same manufacturing process. Although the precise mechanism of action of sipuleucel-T is not known, it appears that the APCs that have taken up PAP-GM-CSF stimulate T cells of the immune system to kill tumor cells that express PAP.

What types of vaccines are being studied in clinical trials?

Vaccines to prevent HPV infection and to treat several types of cancer are being studied in clinical trials.

The list below shows the types of cancer that are being targeted in active cancer prevention or treatment clinical trials using vaccines. If you are accessing this fact sheet online, the cancer names are links to search results from NCI’s clinical trials database.

Active Clinical Trials of Cancer Treatment Vaccines by Type of Cancer:

• Bladder Cancer
• Brain Tumors
• Breast Cancer
• Cervical Cancer
• Hodgkin Lymphoma
• Kidney Cancer
• Leukemia
• Lung Cancer
• Melanoma
• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Pancreatic Cancer
• Prostate Cancer
• Solid Tumors

Active Clinical Trials of Cancer Preventive Vaccines by Type of Cancer:

• Cervical Cancer
• Solid Tumors 

How are cancer vaccines made?

All cancer preventive vaccines approved by the FDA to date have been made using antigens from microbes that cause or contribute to the development of cancer. These include antigens from HBV and specific types of HPV. These antigens are proteins that help make up the outer surface of the viruses. Because only part of these microbes is used, the resulting vaccines are not infectious and, therefore, cannot cause disease.

Researchers are also creating synthetic versions of antigens in the laboratory for use in cancer preventive vaccines. In doing this, they often modify the chemical structure of the antigens to stimulate immune responses that are stronger than those caused by the original antigens.

Similarly, cancer treatment vaccines are made using antigens from cancer cells or modified versions of them. Antigens that have been used thus far include proteins, carbohydrates (sugars), glycoproteins or glycopeptides (carbohydrate-protein combinations), and gangliosides (carbohydrate-lipid combinations).

Cancer treatment vaccines are also being developed using weakened or killed cancer cells that carry a specific cancer-associated antigen or immune cells that are modified to express such an antigen. These cells can come from a patient himself or herself (called an autologous vaccine, such as sipuleucel-T) or from another patient (called an allogeneic vaccine).

Other types of cancer treatment vaccines are made using molecules of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) that contain the genetic instructions for cancer-associated antigens. The DNA or RNA can be injected alone into a patient as a “naked nucleic acid” vaccine, or researchers can insert the DNA or RNA into a harmless virus. After the naked nucleic acid or virus is injected into the body, the DNA or RNA is taken up by cells, which begin to manufacture the tumor-associated antigens. Researchers hope that the cells will make enough of the tumor-associated antigens to stimulate a strong immune response.

Scientists have identified a large number of cancer-associated antigens, several of which are now being used to make experimental cancer treatment vaccines. Some of these antigens are found on or in many or most types of cancer cells. Others are unique to specific cancer types (1, 5, 6, 18–22).

Can researchers add ingredients to cancer vaccines to make them work better?

Antigens and the substances discussed in Question 10 are often not strong enough inducers of the immune response to make effective cancer treatment vaccines. Researchers often add extra ingredients, known as adjuvants, to treatment vaccines. These substances serve to boost immune responses that have been set in motion by exposure to antigens or other means. Patients undergoing experimental treatment with a cancer vaccine sometimes receive adjuvants separately from the vaccine itself (23).

Adjuvants used for cancer vaccines come from many different sources. Some microbes, such as the bacterium Bacillus Calmette-Guérin (BCG) originally used as a vaccine against tuberculosis, can serve as adjuvants (24). Substances produced by bacteria, such as Detox B, are also frequently used. Biological products derived from nonmicrobial organisms can be used as adjuvants, too. One example is keyhole limpet hemocyanin (KLH), which is a large protein produced by a sea animal. Attaching antigens to KLH has been shown to increase their ability to stimulate immune responses. Even some nonbiological substances, such as an emulsified oil known as montanide ISA–51, can be used as adjuvants.

Natural or synthetic cytokines can also be used as adjuvants. Cytokines are substances that are naturally produced by white blood cells to regulate and fine-tune immune responses. Some cytokines increase the activity of B cells and killer T cells, whereas other cytokines suppress the activities of these cells. Cytokines frequently used in cancer treatment vaccines or given together with them include interleukin 2 (IL2, also known as aldesleukin), interferon alpha (INF–a), and GM–CSF, also known as sargramostim (see Question 8).

Do cancer vaccines have side effects?

Vaccines intended to prevent or treat cancer appear to have safety profiles comparable to those of traditional vaccines (6). However, the side effects of cancer vaccines can vary among vaccine formulations and from one person to another.

The most commonly reported side effect of cancer vaccines is inflammation at the site of injection, including redness, pain, swelling, warming of the skin, itchiness, and occasionally a rash.

People sometimes experience flu-like symptoms after receiving a cancer vaccine, including fever, chills, weakness, dizziness, nausea or vomiting, muscle ache, fatigue, headache, and occasional breathing difficulties. Blood pressure may also be affected.

Other, more serious health problems have been reported in smaller numbers of people after receiving a cancer vaccine. These problems may or may not have been caused by the vaccine. The reported problems have included asthma, appendicitis, pelvic inflammatory disease, and certain autoimmune diseases, including arthritis and systemic lupus erythematosus.

Vaccines, like any other medication affecting the immune system, can cause adverse effects that may prove life threatening. For example, severe hypersensitivity (allergic) reactions to specific vaccine ingredients have occurred following vaccination. However, such severe reactions are quite rare.