Cancer Vaccine Primer

How immune cells are activated to attack foreign invaders

How immune cells are activated to attack foreign invaders

Key Points

  • Cancer vaccines are intended either to treat existing cancers
    (therapeutic vaccines) or to prevent the development of cancer
    (prophylactic vaccines).
  • Therapeutic vaccines, which are administered
    to cancer patients, are designed to treat cancer by stimulating
    the immune system to recognize and attack human cancer cells without
    harming normal cells.  Prophylactic vaccines, on the other hand,
    are given to healthy individuals to stimulate the immune system
    to attack cancer-causing viruses and prevent viral infection.
  • The only cancer vaccine licensed by the FDA is a prophylactic
    vaccine against hepatitis B virus, an infectious agent associated
    with liver cancer.
  • Scientists are currently evaluating
    several different vaccines in large human trials to determine
    which approaches are most effective for particular kinds of cancers.

  1. What is a cancer vaccine?

    Cancer vaccines are intended either to treat existing cancers (therapeutic vaccines)
    or to prevent the development of cancer (prophylactic vaccines).  Both types
    of vaccines have the potential to reduce the burden of cancer.  Treatment or
    therapeutic vaccines are administered to cancer patients and are designed to
    strengthen the body’s natural defenses against cancers that have already developed.
    These types of vaccines may prevent the further growth of existing cancers,
    prevent the recurrence of treated cancers, or eliminate cancer cells not killed
    by prior treatments.  Prevention or prophylactic vaccines, on the other hand,
    are administered to healthy individuals and are designed to target cancer-causing
    viruses and prevent viral infection.

  2. Is any cancer vaccine currently available in the United States?

    Yes.  The single cancer vaccine licensed by the Food and Drug Administration
    is a prophylactic vaccine against hepatitis B virus, an infectious agent associated
    with liver cancer.  There are no licensed therapeutic vaccines to date.  However,
    several treatment vaccines are in large-scale testing in humans.  If clinical
    trial results are favorable, additional cancer vaccines may be approved for
    use in the United States within the next few years.

  3. How are therapeutic vaccines designed to treat cancer?

    Vaccines used to treat cancers take advantage of the fact
    that certain molecules on the surface of cancer cells are either unique or more
    abundant than those found on normal or non-cancerous cells.  These molecules,
    either proteins or carbohydrates, act as antigens, meaning that they can stimulate
    the immune system to make a specific immune response.  Researchers hope that
    when a vaccine containing cancer-specific antigens is injected into a patient,
    these antigens will stimulate the immune system to attack cancer cells without
    harming normal cells.

  4. Why does the immune system need a vaccine to help fight cancer?

    The immune system generally doesn’t “see” tumors as dangerous or foreign, and
    doesn’t mount a strong attack against them.  One reason tumor molecules do not
    stimulate an effective immune response may be that tumor cells are derived from
    normal cells.  So, even though there are many molecular differences between
    normal cells and tumor cells, cancer antigens are not truly foreign to the body,
    but are normal molecules, either altered in subtle ways or more abundant.

    Another reason tumors may not stimulate an immune response is that cancer cells
    have developed ways to escape from the immune system.  Scientists now understand
    some of these tricks, which include shedding tumor antigens, and reducing the
    number of molecules and receptors that the body normally relies on to activate
    T cells (specific immune cells) and other immune responses.  Reducing these
    molecules makes the immune system less responsive to the cancer cells; the tumor
    become less “visible” to the immune cells.  Hopefully, this knowledge can be
    used by researchers to design more effective vaccines.

  5. What strategies are used to design effective cancer treatment vaccines?

    Researchers have developed several strategies to stimulate an immune response
    against tumors.  One is to identify unusual or unique cancer cell antigens that
    are rarely present on normal cells.

    Other techniques involve making the tumor-associated antigen more immunogenic,
    such as (a) altering its amino acid structure slightly, (b) placing the gene
    for the tumor antigen into a viral vector (a harmless virus that can be used
    as a vehicle to deliver genetic material to a targeted cell), and (c) adding
    genes for one or more immuno-stimulatory molecules into vectors along with the
    genes for the tumor antigen.

    Another technique is to attach something that is definitely foreign, known as
    an adjuvant, to tumor molecules (see Question 8).  By using the adjuvant as a
    decoy, the immune system may be tricked into attacking both the antigen/adjuvant
    complex (the vaccine) and the patient’s tumor.

  6. What types of treatment vaccines are currently under investigation?

    The types of vaccines listed below represent various methods investigators have
    devised for presenting cancer antigens to the body’s immune system.  This list
    is not meant to be comprehensive.

    Antigen/adjuvant vaccines
    Antigen vaccines were some of the first cancer vaccines investigated.  Antigen
    vaccines commonly use specific protein fragments or peptides to stimulate the
    immune system to fight tumor cells.  One or more cancer cell antigens are combined
    with a substance that causes an immune response, known as an adjuvant.  A cancer
    patient is vaccinated with this mixture.  It is expected that the immune system,
    in responding to the antigen-carrying adjuvant, will also respond to tumor cells
    that express that antigen.

    Whole cell tumor vaccines
    Taken either from the patient’s own tumor (autologous) or tumor cells from one
    or more other patients (allogeneic), these whole cell vaccine preparations contain
    cancer antigens that are used to stimulate an immune response.

    Dendritic cell (DC) vaccines
    Specialized white blood cells known as dendritic cells (DCs) are taken from
    a patient’s blood through a process called
    In the laboratory, the DCs are stimulated with the patient’s own cancer antigens,
    grown in petri dishes, and re-injected into the patient.  Once injected, DC
    vaccines activate the immune system’s T cells.  Activation by DCs is expected
    to cause T cells to multiply and attack tumor cells expressing that antigen.

    Viral vectors and DNA vaccines
    Viral vectors and DNA vaccines use the nucleic acid sequence of the tumor antigen to produce the cancer
    antigen proteins. The DNA containing the gene for a specific cancer antigen is manipulated in the
    laboratory so that it will be taken up and processed by immune cells called antigen-presenting cells (APCs).
    The APC cells then display part of the antigen together with another molecule
    on the cell surface.  The hope is that when these antigen-expressing APC cells
    are injected into a person, the immune system will respond by attacking not
    only the APC cells, but also tumor cells containing the same antigen.  Vector-based and
    DNA vaccines are attractive because they are easier to manufacture than some other vaccines.

    Idiotype vaccines
    Since antibodies are molecules containing protein and carbohydrate, they can
    themselves act as antigens and induce an antibody response.  Antibodies produced
    by certain cancer cells (i.e., B-cell lymphomas and myelomas), called idiotype
    antibodies, are unique to each patient and can be used to trigger an immune
    response in a manner similar to antigen vaccines.

  7. Which antigens are commonly found in cancer vaccines?

    Cancer cell antigens may be unique to individual tumors, shared by several tumor
    types, or expressed by the normal tissue from which a tumor grows.  In 1991,
    the first human cancer antigen was discovered in the cells of a patient with
    metastatic melanoma, a potentially lethal form of skin cancer. The discovery
    led to a flurry of research to identify antigens for other cancers.

    Treatment Vaccines

    Patient-specific vaccines

    Patient-specific vaccines use a patient’s own tumor cells to generate a vaccine
    intended to stimulate a strong immune response against an individual patient’s
    malignant cells.  Each therapy is tumor-specific so, in theory, cells other
    than tumor cells should not be affected.  There are several kinds of patient-specific
    vaccines that use antigens from a patient’s own tumor cells but deliver the
    antigen differently.

    Prostate Specific Antigen (PSA) is a prostate-specific protein
    antigen that can be found circulating in the blood as well as on prostate cancer
    cells.  PSA is present in small amounts in men who do not have cancer, but the
    quantity of PSA generally rises when prostate cancer develops.  Patients
    have been shown to mount T-cell responses to PSA.

    Sialyl Tn (STn) is a small, synthetic carbohydrate that mimics the mucin molecules (the
    primary molecule present in mucus) found on certain cancer cells.

    Heat Shock Proteins (HSPs) (e.g., gp96) are produced
    in cells in response to heat, low sugar levels and other stress signals.  Besides
    protecting against stress, these molecules are also involved in the proper processing,
    folding, and assembling of proteins within cells.  In laboratory experiments,
    HSPs from mouse tumors, in combination with small peptides, protected mice from
    developing cancer.  The human vaccine consists of heat shock protein and associated
    peptide complexes isolated from a patient’s tumor.  HSPs are under investigation
    for treatment of several cancers including liver, skin, colon, lung, lymphoma
    and prostate cancers.

    Ganglioside molecules  (e.g., GM2, GD2, and GD3) are complex molecules
    containing carbohydrates and fats.  When ganglioside molecules are incorporated
    into the outside membrane of a cell, they make the cell more easily recognized
    by antibodies.  GM2 is a molecule expressed on the cell surface of a number
    of human cancers.  GD2 and GD3 contain carbohydrate antigens expressed by human
    cancer cells.

    Carcinoembryonic antigen (CEA) is found in high levels in people with colorectal, lung, breast
    and pancreatic cancer as compared with normal tissue. CEA
    is thought to be released into the bloodstream by tumors.  Patients
    have been shown to mount T-cell responses to CEA.

    MART-1 (also known as Melan-A) is an antigen expressed
    by melanocytes — cells that produce melanin, the molecule responsible for the
    coloring in skin and hair.  It is a specific melanoma cancer marker that is
    recognized by T cells and more abundant on melanomas than normal cells.

    Tyrosinase is a key enzyme involved in the initial stages of
    melanin production.  Studies have shown that tyrosinase is a specific marker
    for melanoma and more abundant on melanomas than normal cells.

    Prevention Vaccines

    Viral proteins on the outside coat of the cancer-causing viruses are
    commonly used as antigens to stimulate the immune system for prevention vaccines.

  8. What are adjuvants?   Which adjuvants are commonly used in treatment vaccines?

    To heighten the immune response to cancer antigens, researchers
    usually attach a decoy substance, or adjuvant, that the body will recognize
    as foreign.  Adjuvants are weakened proteins or bacteria which “trick”
    the immune system into mounting an attack on both the decoy and the tumor cells.
    Several adjuvants are described below:

    Keyhole limpet hemocyanin (KLH) is a
    protein made by a shelled sea creature found along the coast of California and
    Mexico known as a keyhole limpet.  KLH is a large protein that both causes an
    immune response and acts as a carrier for cancer cell antigens.  Cancer antigens
    often are relatively small proteins that may be invisible to the immune system.
    KLH provides additional recognition sites for immune cells known as T-helper-cells
    and may increase activation of other immune cells known as cytotoxic T-lymphocytes

    Bacillus Calmette Guerin (BCG) is an inactivated form of the
    tuberculosis bacterium routinely used for decades to vaccinate against TB.
    BCG is added to some cancer vaccines with the hope that it will boost the immune
    response to the vaccine antigen.  It is not well understood why BCG may be especially
    effective for eliciting immune response.  However, BCG has been used for years
    with other vaccines, including the vaccine for tuberculosis.

    Interleukin – 2 (IL-2) is a protein made by the body’s immune
    system that may boost the cancer-killing abilities of certain specialized immune
    system cells called natural killer cells.  Although it can activate the immune
    system, many researchers believe IL-2 alone will not be enough to prevent cancer
    relapse.  Several cancer vaccines use IL-2 to boost immune response to specific
    cancer antigens.

    Granulocyte Monocyte-Colony Stimulating Factor (GM-CSF) is a protein that stimulates the proliferation of antigen-presenting cells.

    QS21 is a plant extract that, when added to some vaccines, may improve the immune response.

    Montanide ISA-51 is an oil-based liquid intended to boost an immune response.

  9. Why are some vaccines used to treat specific kinds of cancer?

    Many cancer vaccines treat only specific types of cancers
    because they target antigens found on specific cancers.  For example, a vaccine
    against prostate cancer may be able to attack cancer cells within the prostate
    itself or cells that have spread to other parts of the body, but would not affect
    cancers originating in other tissues.

    Vaccines that target antigens found on several different
    kinds of cancer cells are used to treat multiple cancers.  The effectiveness
    of the vaccine would be expected to differ according to the amount of antigen
    on different kinds of cancer cells.  Researchers also are investigating a possible
    “universal” cancer vaccine that might cause an immune response against cancer
    cells that originate from any tissue.

  10. Are there vaccines under development to prevent cancer?

    Yes, some vaccines currently under investigation have the potential to reduce
    the risk of cancer. These vaccines target infectious agents that cause
    cancer and are similar to traditional prophylactic vaccines, which target other
    disease-causing infectious agents such as those that cause polio or measles.
    Non-infectious components of cancer-causing viruses, commonly the viral coat
    proteins (proteins on the outside of the virus), serve as antigens for these
    vaccines.  It is hoped that these antigens will stimulate the immune system
    in the future to attack cancer-causing viruses, which should, in turn, reduce
    the risk of the associated cancer.

    For example, the human papilloma virus (HPV) causes nearly all cases of cervical
    cancer.  Preventing infection by HPV is expected to dramatically reduce the
    risk of cervical cancer.  One promising vaccine against HPV is expected to enter
    large-scale human trials in the near future.  Another promising prevention vaccine
    targets the hepatitis C virus, linked to the development of liver cancer.

  11. Which vaccines have reached Phase III testing?

    The results from ongoing Phase III trials, listed in the table below, will determine
    whether vaccines will play a role in the treatment and prevention of different
    cancers.  The information is derived from government
    databases including the National Cancer Institute’s clinical trials database,,
    and the National Institute’s of Health clinical trials Web site,
    Information on each trial can also be obtained by clicking the link in the far
    right column of the table below.

    Click to view Phase III Vaccine Trials

Further information about cancer vaccines can be found at:

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