![](https://webarchive.library.unt.edu/eot2008/20090131031335im_/http://nci.nih.gov/images/spacer.gif) |
![](https://webarchive.library.unt.edu/eot2008/20090131031335im_/http://nci.nih.gov/images/spacer.gif) |
Search Fact Sheets by Keyword |
![](https://webarchive.library.unt.edu/eot2008/20090131031335im_/http://nci.nih.gov/images/spacer.gif) |
![](https://webarchive.library.unt.edu/eot2008/20090131031335im_/http://nci.nih.gov/images/spacer.gif) |
![](https://webarchive.library.unt.edu/eot2008/20090131031335im_/http://nci.nih.gov/images/spacer.gif) |
|
![](https://webarchive.library.unt.edu/eot2008/20090131031335im_/http://nci.nih.gov/images/spacer.gif) |
![](https://webarchive.library.unt.edu/eot2008/20090131031335im_/http://nci.nih.gov/images/spacer.gif) |
|
|
![](https://webarchive.library.unt.edu/eot2008/20090131031335im_/http://nci.nih.gov/images/spacer.gif) |
|
Cancer Vaccine Fact Sheet
-
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.
-
What cancer-related vaccines are currently available in the United States?
At this time, two vaccines have been licensed by the U.S. Food and Drug
Administration to prevent virus infections that can lead to cancer: the
hepatitis B vaccine, which prevents infection with the hepatitis B virus, an
infectious agent associated with some forms of liver cancer; and GardasilTM,
which prevents infection with the two types of human papillomavirus (HPV) - HPV
16 and 18 -- that together cause 70 percent of cervical cancer cases worldwide.
Gardasil also protects against infection with HPV types 6 and 11, which account
for 90 percent of cases of genital warts.
There are no licensed therapeutic vaccines to date. However, several treatment
vaccines are in large-scale testing in humans.
-
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.
-
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. Therefore, 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 modes of escape, 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 becomes less "visible" to the immune cells.
Scientists hope that this knowledge can be used by researchers to design more
effective vaccines.
-
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, or more likely to cause an immune
response, 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 clearly 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.
-
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 leukapheresis. 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 that express 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
Because antibodies contain proteins and carbohydrates, 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.
-
Which antigens are commonly found in cancer vaccines under investigation?
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 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 under investigation that use antigens from a
patient's own tumor cells.
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 generally is present in small amounts in men who do not have
cancer, but the quantity of PSA generally rises when prostate cancer develops.
The higher a man's PSA level, the more likely it is that cancer is present, but
there are many other possible reasons for an elevated PSA level. 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. In addition to
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 on
tumors 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 is more abundant on melanoma cells
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 is more abundant on melanoma cells than normal cells.
Prevention Vaccines
Viral proteins on the outside coat of cancer-causing viruses
are commonly used as antigens to stimulate the immune system to prevent
infections with the viruses.
-
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 (CTLs).
Bacillus Calmette Guerin (BCG) is an inactivated form of the
tuberculosis bacterium. 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 decades 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 body's immune response.
Montanide ISA-51 is an oil-based liquid intended to boost an
immune response.
-
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.
-
Are there other vaccines under development to prevent cancer?
Yes, in addition to the FDA-approved Hepatitis B vaccine and HPV vaccine, there
are other vaccines currently under investigation that have the potential to
reduce the risk of cancer. These vaccines target infectious agents that cause
cancer, similar to traditional prophylactic vaccines that 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.
-
Which vaccines have reached Phase III testing?
The results from ongoing or unpublished Phase III trials, listed in the table
below, will determine what role vaccines will play in the treatment and
prevention of different cancers. The information is derived from government
databases including the National Cancer Institute's clinical trials database,
http://cancer.gov/clinicaltrials/search, and the National Institutes of
Health clinical trials Web site, http://clinicaltrials.gov.
Information about each trial also can be obtained by clicking the links in the
far right column of the table.
Type of Cancer
|
Title of Study
|
Vaccine Name (if applicable)
|
Lead Institution
|
Nature of Vaccine
|
Purpose of the Study
|
Study Start Date, Links, and Status |
Cervical Cancer
|
|
GardasilTM HPV (human papilloma virus) quadrivalent vaccine
|
Merck & Co.
|
The HPV quadrivalent vaccine contains viral proteins from four HPV types: HPV
16 & 18, the types that account for about 70% of the worldwide cases of
cervical cancer, and HPV 6 & 11, the types most commonly associated with
genital warts.
|
To see whether the vaccine prevents HPV cervical infection,
precancerous cervical lesions, and genital warts.
|
2002
NCT00092521
This trial is no longer accepting patients.
|
Cervical Cancer
|
HPV16/18 Vaccine Trial in Costa Rica
|
CervarixTM HPV bivalent vaccine
|
National Cancer Institute (in collaboration with Costa Rican
investigators) |
The HPV bivalent vaccine (provided to NCI for this trial by GlaxoSmithKline
Biologicals) contains viral proteins from two HPV types: HPV 16 & 18, the types
that account for about 70% of the worldwide cases of cervical cancer.
|
To see whether the vaccine prevents persistent HPV cervical
infection and precancerous cervical lesions, to examine the duration of
protection seen with the vaccine, and to evaluate other issues that might
increase our understanding of vaccines, immune responses to vaccines, and
cervical cancer. |
2004
NCT00128661
PDQ Summary (NCI-04-C-N191)
|
Follicular B-cell Non-Hodgkin's Lymphoma
|
Randomized Trial of Patient-specific Vaccination With Conjugated
Follicular Lymphoma-derived Idiotype Proteins With Local GM-CSF in First
Complete Remission |
Biovaxid®
|
National Cancer Institute
|
The vaccine is composed of antibodies that are unique to a
patient's own tumor cells. These idiotype proteins are chemically attached to
the adjuvant protein keyhole limpet hemocyanin (KLH). GM-CSF (granulocyte
macrophage colony stimulating factor) is used to enhance the immune response
against the idiotype proteins.
|
To compare two vaccination groups: group I patients receive
injections of the vaccine plus GM-CSF; group II patients receive injections
containing only KLH and GM-CSF.
|
January 2000
NCT00096577
PDQ Summary (BIOVEST-BV301)
This trial is currently accepting patients.
|
Follicular B-cell Non-Hodgkin's Lymphoma
|
Combination Chemotherapy Followed by Vaccine Therapy Plus
Sargramostim in Treating Patients With Stage III or Stage IV Non-Hodgkin's
Lymphoma
|
GTOP-99 MyVax® Personalized Immunotherapy
|
Genitope Corporation
|
The vaccine consists of antibodies that are unique to a patient's
tumor. These idiotype proteins are chemically attached to the adjuvant protein
KLH. Sargramostim (GM-CSF) is also used to enhance the immune response.
|
To evaluate time to tumor progression in patients who receive
vaccines compared to controls, who receive adjuvant alone and GM-CSF alone.
|
November 2000
NCT00017290
PDQ Summary
(GENITOPE-G2000-03)
This trial is no longer accepting patients.
|
Kidney Cancer
|
Survival Study of Oncophage® vs. Observation in Patients With
Kidney Cancer
|
OncophageTM (HSPPC-96)
|
Antigenics, Inc.
|
The vaccine -- heat shock protein (gp96) and associated peptides -- is made
from each patient's own tumor.
|
To determine whether patients receiving Oncophage treatment for
surgically removed non-metastatic renal cell carcinoma survive longer than
patients who do not receive vaccine treatment.
|
December 2002
NCT00033904 (Part 1)
PDQ Summary (C-100-12
Part I)
This trial is no longer accepting patients.
NCT00126178 (Part 2)
This trial was terminated by the sponsor.
|
Cutaneous Melanoma
|
Study of Heat Shock Protein-Peptide Complex (HSPPC-96) vs.
IL-2/DTIC for Stage IV Melanoma |
OncophageTM (HSPPC-96)
|
Antigenics, Inc.
|
The vaccine -- heat shock protein (gp96) and associated peptides
-- is made from each patient's own tumor.
|
To determine whether people with metastatic melanoma who receive
Oncophage after surgery live longer than people who may or may not have surgery
but who receive conventional chemotherapy including interleukin-2
(IL-2)/dacarbazine /temozolomide-based therapy.
|
March 2002
NCT00039000
PDQ Summary (C-100-21)
This trial is no longer accepting patients.
|
Cutaneous Melanoma
|
Vaccine Therapy in Treating Patients With Primary Stage II
Melanoma
|
Not Named
|
European Cooperative (EORTC)
|
The vaccine consists of GM2, a common antigen on melanoma cells,
which is conjugated to the adjuvant KLH. QS21 is used to enhance the immune
response.
|
To compare the disease-free and overall survival of stage II
melanoma patients receiving the vaccine to those not receiving the vaccine.
|
February 2002
NCT00005052
PDQ Summary (EORTC-18961)
This trial is no longer accepting patients.
|
Cutaneous Melanoma |
Vaccine Therapy and/or Sargramostim in Treating Patients With Locally or
Advanced Metastatic Melanoma |
Not Named
|
National Cancer Institute
|
The vaccine contains a combination of three melanocyte-specific
antigens: tyrosinase, gp100, and MART. Sargramostim (GM-CSF) is used to enhance
the immune response.
|
To determine the effectiveness of peptide vaccine therapy and/or
GM-CSF in treating patients with locally advanced or metastatic melanoma.
|
December 1999
NCT00005034
PDQ Summary (ECOG-4697)
This trial is currently accepting patients.
|
Cutaneous Melanoma
|
Phase III Multi-Institutional Randomized Study of Immunization
With the gp100: 209-217 (210M) Peptide Followed by High Dose IL-2 vs. High-Dose
IL-2 Alone in Patients With Metastatic Melanoma |
Not Named
|
National Cancer Institute
|
The vaccine contains gp100, IL-2, and Montanide ISA-51. Montanide
ISA-51 is an oil used to enhance the immune response.
|
Since high-dose IL-2 is currently approved by the FDA for treating
patients with metastatic melanoma, the protocol will compare the use of the
vaccine plus IL-2 to IL-2 alone.
|
February 1999
PDQ Summary
(CCCGHS-NCI-T98-0085)
This trial is currently accepting patients.
|
Cutaneous Melanoma |
MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination
Treatment for Patients With Melanoma
|
MDX-1379 |
Medarex, Inc.
|
The vaccine contains gp100. MDX-010 is an anti-cytotoxic T
lymphocyte antigen-4 (CTLA-4) monoclonal antibody, also known as ipilumumab.
CTLA-4 helps suppress immune responses; blocking its activity with MDX-010 may
improve the immune response induced by MDX-1379.
|
To determine the safety and effectiveness of MDX-010 in
combination with MDX-1379 in patients with previously treated, unresectable
stage III or IV melanoma. Survival time will be evaluated, as well as patient
responses and time to disease progression.
|
September 2004
NCT00094653
PDQ Summary (MDX010-20)
This trial is currently accepting patients
|
Ocular Melanoma
|
Vaccine Therapy in Treating Patients With Melanoma of the Eye
|
Not Named
|
European Cooperative (EORTC)
|
The vaccine contains several melanoma differentiation peptides.
|
To determine the effectiveness of vaccine therapy in preventing
liver metastasis and increasing survival in patients at high risk for recurrent
melanoma of the eye.
|
February 2002
NCT00036816
PDQ Summary (EORTC-18001)
This trial is no longer accepting patients.
|
Prostate Cancer
|
GVAX® Vaccine for Prostate Cancer Versus Docetaxel and
Prednisone in Patients With Metastatic Hormone-Refractory Prostate Cancer
|
GVAX®
|
Cell Genesys, Inc.
|
Cells from two, patient-non-specific prostate cancer cell lines
that have been genetically engineered to overexpress and secrete GM-CSF, which
stimulates the immune response to vaccines.
|
The purpose of this study is to compare the survival of patients
receiving the GVAX® vaccine and the survival of patients receiving
chemotherapy in individuals with prostate cancer who no longer respond to
hormonal therapy, who have documented metastases, and who have not been treated
with chemotherapy in the past.
|
July 2004
NCT00089856
PDQ Summary (G-0029, VITAL-1)
This trial is currently accepting patients
|
Prostate Cancer
|
Docetaxel in Combination With GVAX ® Vaccine Versus Docetaxel
and Prednisone in Prostate Cancer Patients |
GVAX®
|
Cell Genesys, Inc.
|
Cells from two, patient-non-specific prostate cancer cell lines
that have been genetically engineered to overexpress and secrete GM-CSF, which
stimulates the immune responses to vaccines.
|
The purpose this study is to compare the survival of patients
receiving docetaxel in combination with the GVAX® vaccine versus the
survival of patients receiving docetaxel and prednisone in individuals who have
prostate cancer that no longer responds to hormone therapy and who have
documented metastases and cancer-associated pain.
|
July 2004
NCT00133224
PDQ Summary (G-0034, VITAL-2)
This trial is currently accepting patients
|
Prostate Cancer
|
Phase III Randomized Study of APC8015 (Provenge®) in Patients
With Asymptomatic Metastatic Androgen-Independent Adenocarcinoma of the
Prostate
|
Provenge® sipuleucel T
|
National Cancer Institute
|
A patient's own immune system cells trained in the laboratory to
target the protein prostatic acid phosphatase (PAP), which is made by prostate
cells
|
Compare the time to disease progression and the time to the
development of disease-related pain in patients with asymptomatic, metastatic,
androgen-independent adenocarcinoma of the prostate treated with APC8015 versus
placebo.
|
March 2004
NCT00065442
This trial is currently accepting patients
|
Multiple Myeloma
|
A Study of MAGE-A3 and NY-ESO-1 Immunotherapy in Combination With
DTPACE Chemotherapy and Autologous Transplantation in Multiple Myeloma. |
Not Named
|
University of Arkansas
|
Fragments from two tumor proteins called MAGE-A3 and NY-ESO-1,
which are found in myelomas and other tumors and which have been shown to
stimulate antitumor immune responses.
|
Determine whether peptide vaccines will stimulate the immune
system to attack and kill myeloma cells.
|
November 2003
NCT00090493
This trial is currently accepting patients
|
Back to Top |
|
![](https://webarchive.library.unt.edu/eot2008/20090131031335im_/http://nci.nih.gov/images/spacer.gif) |