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Provenge
Approval
May 5, 2007
It is now closing in on 35 years since that meeting and we still
do not have a cancer vaccine on the market. Further, immunotherapy
has had only a marginal impact on cancer treatment. Immune stimulation
has largely been left to the complementary and alternative medicine
practitioners. Unfortunately, herbal immune stimulates simply
do not work at all and are based on laughably simplistic views
of how the immune system actually works.
However, this grim picture may soon change. We now have a robust
understanding of how the immune system can act to control cancer
progression. We have vaccine strategies that work very well in
animal models. There are multiple cancer vaccines in clinical
trial for prostate cancer and others malignancies. At the end
of March, one of these vaccines for prostate cancer, Provenge,
went before the FDA advisory committee and may well attain final
approval in May. In this article, we will explain how this vaccine
works and why it has faced controversy during the approval process.
Most attempts to control cancer via the immune system aim to
use T cells to kill the cancer. You have probably heard of T
cells because the HIV virus destroys them, leading to AIDS. There
are several types of T cells, but the ones involved in killing
cancer cells are the cytotoxic T cells. These cells have the
capacity to recognize and bind to cancer cells, which they then
kill. One of the central problems in immunotherapy was that it
is difficult to generate large numbers of T cells that can specifically
recognize and kill cancer cells.
When T cells recognize a cancer cell target, they do so by binding
to an antigen found on these cells, but not to other normal cells
throughout the body. One key advance has been in the discovery
of how T cells are “trained” to recognize a specific
antigen. This was the result of investigations into an unusual
cell, called the dendritic cell. The dendritic cells take up
the antigen of interest, digest it and present a fragment of
this antigen on their surface. When a T cell at the appropriate
stage of development encounters a dendritic cell bearing an antigen
fragment, it becomes primed to attack any cell bearing this antigen.
Many of the current cancer vaccines involve harvesting the patient’s
blood, isolating the dendritic cells from that blood, and growing
large numbers of that patient’s dendritic cells.
These dendritic cells are then “armed” with the key
antigen fragment and infused back into the patient. These “armed” dendritic
cells then proceed to train large numbers of T cells to attack
the cancer bearing the antigen. Provenge works in just this way.
In this case, the antigen is the prostatic acid phosphatase,
or PAP for short. PAP was the dominant marker used for prostate
cancer before we had the PSA test. It is still of some use in
that its level in the blood only increases when the cancer is
metastatic. The key factor is that it is a protein found for
the most part only on prostate cancer cells.
Click here to read the rest of the article in Volume 10 Issue
1 of Prostate Forum. |
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