5.05.07 Provenge Approval: Immunotherapy For Prostate Cancer From Dendreon, New PC treatment, PCa Immune Response

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.

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