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Targeted Therapies for Prostate Cancer Tutorial

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Therapeutic Vaccines

In This Section:

 

Harnessing the power of the immune system

Although the immune system is programmed to defend the body against invaders such as bacteria or viruses, its ability to fight cancer is limited because it doesn't usually recognize cancer cells as foreign. In fact, some cancers actively suppress the body's immune response.

Shown on the left is an outline of a male body with prostate cancer. On the right is an inset circle coming from the groin area showing a layer of pink normal cells with an embedded mass of green cancer cells. Antibodies do not recognize the prostate cancer cells as foreign, so they do not attract the blue immune cells that could cause the cancer cells to die. Screen text reads: Some cancers actively suppress the body's immune response.

However, prostate cancer cells do differ from normal cells in some important ways. These differences can be used to harness the immune system's power to destroy cancer cells specifically. For example, proteins made by the cells, called antigens, may be more or less abundant on prostate cancer cells when compared to their normal counterparts.

Shown on the left is a green cell labeled Cancerous Prostate Cell with many yellow antigens on its surface. On the right is a pink cell labeled Normal Prostate Cell with far fewer yellow antigens on its surface. The yellow antigens are also labeled.

Therapeutic vaccines combine the body's general immune response, just like one toward a bacterial or viral infection, with an attack on specific prostate cancer antigens.

Shown are three activated immune cells attacking a green cancer cell. The cancer cell is carrying yellow antigens on its surface and the immune cells recognize the antigens as foreign. The immune cell is also parenthetically labeled as a 'Killer T Cell.'

Another challenge in prostate cancer immunotherapy has been the need to generate large numbers of killer T cells that can specifically recognize, target, and kill prostate cancer cells.

One technique to increase the number of killer T cells harnesses an immune cell called the dendritic cell, or antigen presenting cell, to make a prostate cancer vaccine.

Shown is a labeled dendritic cell with multiple waving arms that extend outward.

The blood of the cancer patient is collected and enriched to increase the population of dendritic cells. These cells are then grown in the laboratory in the presence of a protein or part of a protein that is present in or on the patient's tumor cells.

Shown are several dendritic cells. A protein labeled 'Tumor Cell Protein,' also called an antigen, is shown among the dendritic cells.

The patient's dendritic cells digest the protein and transport tiny pieces of it to the cell surface. When the dendritic cells are put back into the patient, they signal certain populations of killer T cells to destroy all cells with the telltale protein, including cancer cells.

Shown is a dendritic cell that has processed the tumor cell protein and is presenting pieces of the protein on its extended arms. One killer T cell is shown touching an arm of the dendritic cell. All three killer T cells have been activated by the dendritic cell to recognize the tumor cell protein as foreign.

 

Provenge® (sipuleucel-T)

Provenge® (generic drug name sipuleucel-T) is the only cancer therapeutic vaccine that has been approved by the FDA to date. It is approved for use in men with metastatic prostate cancer that does not respond to hormone therapy.

Provenge® uses prostatic acid phosphatase, or PAP, as the key antigen. PAP is highly expressed in nearly all prostate cancers and is largely restricted to prostate cells.

Shown in the background is an image of the head and shoulders of a male patient in a hospital bed. Screen title reads: Provenge®. First bullet reads: The only cancer therapeutic vaccine that has been approved by the FDA to date. Second bullet reads: Approved for use in men with metastatic prostate cancer that does not respond to hormone therapy. Third bullet reads: Uses PAP as the key antigen.

Provenge® is prepared by harvesting the patient's blood and enriching for specialized immune cells, called antigen presenting cells, from that blood.

The antigen presenting cells are then exposed to a recombinant antigen consisting of PAP and granulocyte macrophage colony stimulating factor (GM-CSF).

The role of GM-CSF is to prolong the body's general immune response. The role of PAP is to trigger a specific immune response.

Shown is an immune cell called an antigen presenting cell, or dendritic cell. The dendritic cell is approaching a recombinant antigen consisting of a yellow prostatic acid phosphatase (PAP) and a pale pink granulocyte macrophage colony stimulating factor (GM-CSF). The screen title reads: Provenge® Therapeutic Vaccine. Text across the bottom of the screen reads: The role of PAP is to trigger a specific immune response.

The patient's antigen presenting cells digest the antigen and transport tiny pieces of it to the cell surface. Antigen presenting cells that have taken up and processed the PAP–GM–CSF antigen are then infused back into the patient where they stimulate a specific immune response.

Shown is a dendritic cell, or antigen presenting cell, that has digested the recombinant GM-CSF antigen. The dendritic cell is presenting pieces of the antigen on its arms to an immune cell. The immune cell has been activated to recognize the antigen as foreign.

The infused cellular product can activate large numbers of killer T cells that destroy cells expressing the PAP antigen, primarily prostate cancer cells.

Shown on the left is an outline of a male body with a lymphatic system and prostate cancer. A vaccine has been administered and targeted therapy molecules are circulating through the lymphatic system. On the right is an inset circle coming from the groin area showing a layer of pink normal cells with an embedded mass of green prostate cancer cells. The activated blue immune cells recognize the antigens on cancer cells and destroy some of the cells. The dead cancer cells are colored black.

Self Test

Questions

  1. How do therapeutic vaccines work to attack cancer?
    1. They mount a general immune response.
    2. They promote a specific immune response to the cancer cell's antigens.
    3. They make antibodies against the cancer.
    4. Both A and B.

Answers

  1. Correct answer to Question 1:
    1. They mount a general immune response. There is a better answer.
    2. They promote a specific immune response to the cancer cell's antigens. There is a better answer.
    3. They make antibodies against the cancer. Incorrect. The answer is D (both A and B).
    4. Both A and B. Correct.