 | First identify and isolate antigens (protein
fragments) specific to the tumor.
|
| Deliver these tumor antigens into the body in
ways that induce the immune system to recognize and attack cancer
cells.
|
| Add adjuvants to increase immune effects and
attention to the tumor antigens.
|
| Add additional therapies to offset evasion or
protection tactics by cancer cells.
|
| Add treatments to decrease tumor burden and
increase antigen fallout, without compromising immunity.
(Antigens in dying cells could enhance immune response in some
circumstances.)
|
| Alter the immune profile to favor anti-cancer
immune action. An immune profile is the predominance of
types of immune cells and cell signaling.
|
| Alter the expression of cancer cells so that they
become more visible to the immune system. For example, virally
infecting b-cell lymphomas could change how these cells look
to the immune system, making them more immunogenic (capable of
evoking an immune response). |
Targeting tumor cells selectively
Just as we might recognize a criminal by they way he acts or looks (profiling), the immune system has the potential to identify and kill cancers cells because by definition cancer cells express abnormal proteins that distinguish them from normal cells.
Targets: Tumor Associated Antigens (TAA) and Receptors
Tumor Associated Antigens are peptide sequences (fragments of proteins) that make a tumor distinct from normal cells. Tumors
may express unique receptors based on normal or abnormal gene expression.
Two examples of targets based on normal gene expression:
Normal antigen target:
Rituxan targets CD20, which is normally expressed on mature b-cells.
Normal
antigen target: Induce immunity against the Idiotype (Id)
-- a unique marker normally expressed on the surface of the lymphoma
cells that distinguish them from all other lymphocytes and other cells in the body.
The Id, is a receptor
that's specific to an antigen (bacteria, virus, etc.) that particular
immune cell was designed to recognize and kill. The idiotype is
typically clonally expressed, meaning that each malignant cell has
the same idiotype receptor. The goal of Idiotype vaccine treatment is to
"teach" the immune system to target and attack this protein.
Abnormal
antigen target - One example could be if all the
malignant cells were infected by a virus. A vaccine could then
be prepared to "teach" the immune system to recognize and
kill cells that have this viral antigen. We could imagine a therapy
that intentionally infects malignant cells with a virus, and then
induces an immune response against the virus.
The search for tumor antigens is becoming industrialized and automated, and therefore far more efficient.
Some antigen types include: Differentiation antigens, Mutated tumor antigens, Over expressed antigens, Viral antigens
Some technologies that utilize or identify TAAs: DNA chips to identify tumor specific genes, Autologous cell therapy: multiple antigen approach, cross priming of TAAs with antigen presenting cells.
Background Terminology
Antibodies
- are proteins (glycoproteins) with a specific shape that
corresponds to an antigen or cell receptor. B cells produce antibodies
that lock onto pathogens. There are ??
Antigens (Ag) - a general term for a protein or protein fragment considered foreign or abnormal that elicits an immune response in the body.
Epitope - smallest
structural part of an antigen to which an antibody can bind. Also called the
antigenic determinant.
Receptors - A
protein shape on the surface of cells that have a shape specific to an
antigen or protein signal. Both B- and T-cells have surface receptors for
antigens. Each cell has thousands of receptors of a single specificity; that is, with a binding site for a particular
epitope.
Signaling
- Immune cells coordinate actions by sending and receiving
messages.
T-cell receptors (TCRs)
- enable the cell to bind to and, if additional signals are present, to be activated by and respond to an
epitope presented by specialized antigen-presenting cells or
APCs.
B-cell receptors (BCRs) enable the cell to bind to and, if additional signals are present, to be activated by and respond to an
epitope on molecules of a soluble antigen. The response ends with descendants of the B cell secreting vast numbers of a soluble form of its receptors. These are
antibodies.
Humoral Antibody System - B lymphocytes
