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Cancer Vaccines
Advanced Immunotherapy – Fighting
Cancer with Vaccines: Biological
Response Modifiers
“So much exists that is unknown, and this fact
represents a unique opportunity for
investigators, especially young scientists, to
find a foothold and make very important
contributions.” —Philip Vernon, University of
Pittsburgh Cancer Institute
The Need for Cancer Vaccines
Fighting Cancer:
• Treating cancer has historically relied
on a variety of treatments—surgery,
chemotherapy, and radiation—
known “slash, poison, and burn”.
Why use Cancer
Vaccines?
• Cancer vaccines have a potential advantage over these
three options in that the body’s response is longer
lasting (on a scale of years as opposed to weeks or
months), which could possibly eradicate the micrometastases that often linger after standard treatments
end.
Management as
Chronic Disease
• Although cancer eradication wouldn’t be
achieved, vaccines would at least enable
physicians to manage cancer as a chronic
disease.
Two Cancer Vaccine Approaches
Prophylactic Vaccines
•intended to prevent cancer from
developing in healthy people
•target infectious agents that cause or
contribute to the development of cancer.
•Similar to traditional vaccines, which help
prevent infectious diseases by protecting
the body against infection.
•Based on antigens that are carried by
infectious agents and that are relatively
easy for the immune system to recognize as
foreign.
•FDA Approved preventative vaccine:
Gardasil and Cervarix for cervical cancer
Therapeutic Vaccines
•designed to treat cancers that have
already developed.
•intended to delay or stop cancer cell
growth; to cause tumor shrinkage; to
prevent cancer from coming back; or to
eliminate cancer cells that have not
been killed by other forms of treatment.
•FDA approved treatment vaccine:
PROVENGE for treatment of prostate
cancer
Subtypes of Cancer Vaccines
Tumor Vaccines
Dendritic Cell Vaccines
Antigen Vaccines
• Made from tumor cell
preparations: actual cancer
cells that have been
removed during surgery.
• Cells are treated in the lab,
usually with radiation, so
they cannot form more
tumors. In most cases, cells
are changed further by
adding chemicals or new
genes, to make them more
likely to be seen as foreign
by the immune system.
• Cells are then injected into
the patient. The immune
system recognizes antigens
on these cells, then seeks
out and attacks any other
cells with these antigens that
are still in the body.
• Two basic types: allogenic or
autologous
• Autologous vaccines (made
from the person in whom
they will be used), and must
be made individually for
each patient.
• Process used to create them
is complex and expensive.
• Immune cells from the blood
expose d in lab to cancer
cells or cancer antigens, as
well as to other chemicals
that turn them into dendritic
cells and help them grow.
• Dendritic cells are then
injected back into the
patient, where they should
provoke an immune
response to cancer cells in
the body.
• Boost the immune system by
using only one antigen (or a
few), rather than whole
tumor cells that contain
many thousands of antigens.
The antigens are usually
proteins or pieces of
proteins called peptides.
• May be specific for a certain
type of cancer, but they are
not made for a specific
patient like autologous cell
vaccines are.
• Scientists often combine
several antigens in a vaccine
to try to get a stronger
immune response.
DNA Vaccines
Vector-based Vaccines
• Tumor cells or antigens are injected into
the body as a vaccine, they may cause
the desired immune response at first,
but they may become less effective over
time because the immune system
recognizes them as foreign and quickly
destroys them.
• Without any further stimulation, the
immune system returns to its normal
(pre-vaccine) state of activity. To get
around this a steady supply of antigens
to keep the immune response going
must be provided
• Vectors can be given bits of DNA that
code for protein antigens. When the
vectors are then injected into the body,
this DNA might be taken up by cells and
can instruct them to make specific
antigens, which would then provoke the
desired immune response.
• These vaccines use special delivery
systems (called vectors) to make them
more effective: vector-based antigen
vaccines and vector-based DNA
vaccines.
• May be used to deliver more than one
cancer antigen at a time, which may
make the body's immune system more
likely to mount a response.
• Vectors such as viruses and bacteria may
trigger their own immune responses
from the body, which may help make the
overall immune response even stronger.
• Vaccines may be easier and less
expensive to make than some other
vaccines.
Mechanism of Action
•To activate a component of immune system, lymphocytes or
antibodies, against tumor-associated antigens presented by
tumors.
Ultimate Aim
Opportunity
to exploit
Basic
Princinple
•Exploiting peptide recognition by T lymphocytes: sequencing of
peptides derived from MHC molecules has led to the discovery of
allele-specific motifs that correspond to residues that fit into
specific pockets on MHC class I or II molecules. This has allowed for
the discovery of new peptides associated with cancer
•These specific peptides or proteins of the tumor cell that can then
be used to stimulate an immune response included in cancer
vaccine – Synthetic Peptides
•Whole cell (containing tumor antigens) taken from patient or
another patient can be introduced to stimulate immune system to
recognize tumor and mount a response – Cell-based vaccines
Pitfalls in Developing Cancer Vaccines
Irregular and rapid tumor
progress as compared to slow
progress of immune response to
vaccine
Mutation or down
regulation of
immunodominant tumor
antigens – for vaccine to be
effective it must evoke immune
response against a wider range of
antigens
Suppression of immune
response by tumors – e.g. factors
such as TGF-beta, prostaglandins, IL
10 produced by tumor cells may lead
to T cell hypo-responsiveness
Pre-existing treatments like
chemotherapy destroy immune
system to an extent that there’s little
benefit for cancer vaccines to provide
Cancer Vaccines in Development
BiovaxID
Neuvax
HSPPC-96
• produced promising
results in a Phase III
clinical trial of patients
with advanced follicular
lymphoma.
• individualized vaccine that
is made by isolating
proteins from a patient’s
cancer cells and
combining them with a
delivery agent and a
growth factor.
• Once injected, the vaccine
stimulates immune cells to
recognize and fight cancer
cells that may be in the
body.
• Use of BiovaxID
significantly delayed
cancer progression.
• made up of a part of the
HER2 protein called the
E75 peptide. (HER2contributes to the growth
of some breast cancers)
HER2-targeted therapies
such as Herceptin have
dramatically improved
outcomes for women with
HER2-positive breast
cancer.
• Herceptin, NeuVax may
reduce the risk of breast
cancer recurrence.
• has shown promise in the
treatment of glioblastoma
multiforme—an
aggressive type of brain
tumor.
• vaccine is created from
patient’s own tumor cells.
In a Phase II clinical trial of
patients with recurrent
glioblastoma that has
returned after prior
treatment),
Promise of Cancer Vaccines
To date, no specific approach to vaccine therapy has emerged as
clearly superior. Strategies to enhance the immune response will
be the next most important step in therapeutic cancer vaccines.
Identification of the mechanisms by which
cancer cells evade or suppress anticancer
immune responses is pivotal. A better
understanding of how cancer cells
manipulate the immune system could lead to
the development of new drugs that block
those processes and thereby improve the
effectiveness of cancer treatment vaccines.
- Monoclonal antibodies inhibiting T-regs, the
use of a variety of cytokines, and toll-like
receptor stimulation are among the strategies
that will be employed
- Dendritic cells are an extremely appealing
vaccine approach; however, they are limited by
the difficulties associated with patient-specific
cell therapies