How GVAX works

GVAX is similar to traditional vaccines against pathogens like bacteria and viruses. Such traditional vaccines involve the injection of a weakened pathogen or some structural part of it, which is identified and recognized by the immune system. A minor immune response against the vaccine results in immunity towards the pathogen so that next time it enters the body, there will be a swift, strong and systemic response against it. Cell Genesys is taking a similar approach but with some differences. First, the pathogens in this case are cancer cells which are not external pathogens but self derived cells. Second, the vaccine is not given to healthy people but only to people who already have advanced stage prostate cancer. Third, whereas most pathogens can be recognized by the immune system even without any external help, (vaccines simply give the immune system a nice head start), the ultimate goal with GVAX is to make the immune system recognize those cancer cells which it cannot recognize in the first place.

GVAX for Prostate Cancer is comprised of 2 lines of whole prostate tumor cells. These cell lines are considered to be very advanced and malignant so they contain many common antigens (an element recognized by the immune system) found in metastatic prostate c!
ancer. The cells have been modified to constantly produce and secrete granulocyte macrophage colony stimulating factor (GM-CSF). GM-CSF is an important immune stimulatory molecule that leads to the activation of a group of immune cells called Antigen Presenting Cells (APCs). It’s the combination of the antigens GVAX cells express and the GM-CSF they secrete that should generate an effective immune response against prostate tumors.

Before being injected into patients, the cells undergo lethal irradiation in order to prevent them from multiplying, turning them into a scaffold for presenting many cancer related antigens. The basic idea is that once the body’s immune system encounters those GVAX cells, the GM-CSF will stimulate the immune cells to recognize those cells as a threat and initiate an immune response directed at them.

The first stage of the immune response against GVAX is swallowing and processing of the cells by APCs. The next step is the most crucial one, where those APCs migrate to special areas called lymph nodes and present parts of the GVAX cells to other immune system components. By doing so, APCs act as the body’s “intelligence arm”, alerting the immune system that there are unwanted guests in the body and show what they look like.

Once that happens, another type of immune cells called lymphocytes is created and activated. Those lymphocytes can specifically recognize certain antigens that are presented to them by APCs. They are released into the blood stream, looking for those intruders. Upon the encounter with the GVAX cells, the lymphocytes attack and destroy them either by secreting antibodies or by attacking cells with toxic compounds. Hopefully, each patient’s prostate tumor cells will express at least one common antigen with the GVAX cells. As a result, once lymphocytes come across a prostate tumor, they will attack it, even though until that point, the tumor managed to evade the immune system

Using whole cancer cells instead of only structural parts might prove to be a good vaccination vehicle. The GVAX cells express a large repertoire of antigens, as compared to Dendreon’s Provenge , which may prove advantageous. Where Provenge might trigger an immune response against only one specific antigen (However, there is a risk that the immune response triggered by GVAX will not be focused enough; hence, it might be a reaction against a wider spectrum of antigens but also a less potent one.

Another attribute of GVAX is that it is not personalized therapy. Although tumors from different patients share some common antigens, there are differences between tumors each patient bares. The GVAX cells might resemble to the actual tumor cells in the patient’s body, but they are certainly not identical so that might lead to a compromise in specificity. On the other hand, such a universal solution might be much cheaper and simpler to use. There is no need to take anything out of the patient’s body, but simply inject the vaccine. On top of those off-the-shelf qualities, using GVAX might even have an advantage over using each patient’s tumors because one of the main problems of advanced stage tumors is the fact they constantly change via mutations and may even spread to other organs as metastases, which may not be recognized by vaccination using the primary tumor. Using two advanced prostate cancer cell lines for the vaccine might trigger an immune response against those metastases even before they develop.

Another advantage of the GVAX approach is the fact that the first stage of the immune response occurs inside the body (in vivo), the natural environment in which immune cells typically operate in. In the case of Provenge, the initial response occurs in an “antigen cassette” outside the body.

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