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Cancer immunotherapies represent an innovative potential
cancer therapy—a therapy that seeks to harness the body's own defenses to fight the
uncontrolled growth and spread of cancer cells.
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The immune system
has the ability to recognize the difference between "self"
and "non self," that which is and is not a naturally
occurring molecule in the body. In the case of cancer, the difference
between cancer cells and normal healthy cells is sometimes so
slight that they go unnoticed by the immune system and no response
occurs, or the immune system is overwhelmed. The body is "tolerant"
of the cells allowing them to multiply in the body. Cancer immunotherapies
seek to "break" this tolerance.
Cancer immunotherapies are designed to introduce molecules expressed
on cancer cells into the body in a new way that awakens the
immune system to respond and destroy the cancer cell. These
immunotherapies attract immune cells such as dendritic cells that engulf
the vaccine cells which include "antigens" or proteins
on their cell surfaces, and then present (exhibit) fragments
of these antigens. These immune cells, known as "antigen
presenting cells" (APCs), then signal other immune cells
to mature and attack the specific invading antigen. Lymphocytes,
including helper T cells, killer T cells, and B cells, are called
into action. Helper T cells release cytokines, chemical messages
that recruit other immune cells, and killer T cells engulf the
antigen (and the cell it is attached to) the APCs presented
to it. In addition to awakening the cellular side of the immune
system to the tumor cell, some cancer immunotherapies stimulate the
humoral side of the immune system, which includes antibodies,
into action as well. |
Types of Cancer immunotherapies
Research and development efforts are currently under way to develop
therapeutic cancer immunotherapies for the treatment of multiple forms of
cancers. Currently, there are two primary approaches being explored
in the development of making cancer immunotherapies—the "antigen-specific"
approach, and the "whole cell" approach.
Antigen-Specific Approach
The antigen-specific approach seeks to make an immunotherapy that stimulates
an immune response to a specific antigen or antigens that are believed
to be unique to a specific type of tumor. This approach may result
in a highly specific antitumor response, however it poses the challenge
of successfully identifying the specific antigens that are most highly
expressed on a given tumor. Failure to identify the appropriate antigens
could result in lower or no efficacy.
One approach to developing an antigen-specific vaccine involves the
removal and isolation of a patient's dendritic cells, one type of
APC. The dendritic cells are exposed to antigens that are believed
to be associated with a specific tumor type, and are given time to
ingest, process, and "present" the antigens. The cells are
then reintroduced into the patient in vaccine form.
Whole Cell Approach
The whole cell approach uses whole cancer cells to make the vaccine,
not just a specific antigen. Since whole cells express multiple—sometimes
thousands of—antigens, there is potentially a greater chance
of stimulating an immune response since this approach does not require
choosing specific antigens which may or may not turn out to be appropriate
for the patient. Cell Genesys is pursuing a whole cell vaccine approach
with its GVAX® cancer immunotherapies.
Whole cell immunotherapies can be either patient-specific (made completely
from the individual's own tumor cells), non patient-specific (made
from a "cell line"—tumor cells that are grown in a
laboratory), or a mixture of the two. Patient-specific immunotherapies may
offer some advantages over non patient-specific immunotherapies when treating
cancers that involve many different cell types with few like characteristics
(e.g. non small-cell lung cancer). Using the patient's own tumor cells
may increase the likelihood of creating an individualized vaccine
that effectively stimulates an immune response against all cell types
associated with specific form of cancer being treated.
Activating an Immune Response
While some cancer immunotherapies are designed to stimulate an immune response
based solely on the presence of antigens, others are being developed
that utilize antigens as well as cytokines to mount an attack against
cancer cells. Cytokines are chemical messages that stimulate other
immune cells to attack antigens. Some researchers are exploring the
idea of creating immunotherapies comprised of cells that have been genetically
modified to secrete a cytokine such as GM-CSF, interleukins, and interferons.
The presence of these cytokines may potentially help "jump start"
the immune system to launch a more robust and efficacious immune response.
Possible Benefits of Cancer immunotherapies
In addition to providing a new treatment option for patients who have
failed other therapies, clinical data suggest that cancer immunotherapies
may offer therapeutic advantages over existing therapies:
1. Favorable Side Effect Profile:
Unlike many traditional cancer treatments such as chemotherapy and
radiation therapy, cancer immunotherapies have generally been associated
with very few serious side effects. This favorable side effect profile may
potentially enable patients to maintain a higher quality of life during
the course of treatment.
2. Combination Therapy: Numerous
clinical trials are being conducted evaluating the use of cancer immunotherapies
in combination with other traditional therapies such as chemotherapy,
radiation therapy, and stem cell transplantation. Combination therapies
offer the potential of improving/enhancing the efficacy of these traditional
treatments.
The Current State of Cancer immunotherapies
Research and development efforts are currently under way at numerous
organizations to thoroughly evaluate the safety and efficacy of different
approaches to cancer immunotherapies. Currently, cancer immunotherapies are being
evaluated in multiple human clinical trials for many types of cancer
and are available only in the clinical trial setting.
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