What Makes CEGE’s GVAX Unique?

 

One of the most important features in GVAX is its universality. The concept behind GVAX is applicable to numerous cancer types, since theoretically, any type of cancer cell can be genetically modified to secrete GM-CSF, making it a potential cancer vaccine. For example, in order to create GVAX for pancreatic cancer, Cell Genesys chose a pancreatic cancer cell-line, inserted the GM-CSF gene into the cells, irradiated them and the vaccine was ready. For the treatment of leukemia, the company did the same with leukemia cells and so on. However, each type of cancer includes so many types of available cell-lines, that choosing the right cell-line is of extremely high importance. Furthermore, since it is possible to combine more than one cell-line per vaccine, GVAX’s diversity potential, as a platform, is tremendous.

 

Another apparent advantage is the fact that in GVAX’s case, all the stages of the immune response occur inside the patient’s body. The first stage of every anti-cancer immune response involves the exposure of a special group of immune cells, called Antigen Presenting Cells (APCs) to cancer antigens. This exposure is the basis of enhancing any immune response, making it extremely crucial. Some cancer vaccines like Dendreon’s Provenge and Northwest’s Biotherapeutics DCVax, involve taking out APCs from the patient’s body and conducting the exposure stage in vitro (outside of the body). These activated cells are then re-administered into each patient and will hopefully ignite a specific immune response against cancer cells inside the body. Cell Genesys takes a different approach, similar to that of traditional vaccines, by injecting patients with the cancer antigens themselves (in the form of cancer cells). Thus, the immune cells are exposed to the cancer antigens in vivo (inside the body), in their natural environment. Both approaches have demonstrated clinical activity, however, considering the astounding complexity of biological systems and the huge success conventional vaccines have had, “keeping it natural” simply looks like a better idea.

An additional key differentiator of GVAX is its multi-antigen approach. While many cancer vaccines are aimed at manifesting an immune response against a specific cancer-related antigen, Cell Genesys is using whole cancer cells as antigens. Each cancer cell has countless potential antigens that can be targeted by the immune system. By using whole cancer cells, and sometimes even more than one strain, the amount of potential cancer antigens is immense. Thus, the immune response generated by GVAX might be less focused, but much broader and has the potential of impacting a wider population of cancer cells. In contrast to what many think, the population of cancer cells in a patient’s body is very heterogeneous. In many cases, different cancer cells from the same tumor may present different sets of antigens, especially in more advanced stages of the disease. Stimulating the immune system to recognize multiple antigens may result in a response against cancer cells, which would otherwise evade a single-antigen oriented immune response. Furthermore, scientists postulate that there are still a lot of undiscovered cancer-related antigens. By using whole cancer cells, GVAX enables an immune response against unknown as well as known cancer-related antigens. The beauty of this approach is that drug developers don’t have to know specifically which antigens trigger an immune response, as long as the job is done by the immune system.

Most cancer vaccines involve antigens which are not presented to the immune system in their fully natural state, i.e. on the surface of cancer cells. These antigens are often referred to as recombinant antigens. For example, Dendreon uses a recombinant version of prostatic acid phosphatase (PAP), an antigen present in the vast majority of prostate tumors. In GVAX’s case, the cancer-related antigens are presented to the immune system on real cancer cells, in their original conformation. Hence, the chances for accurate recognition of cancer antigens and immune response channeling towards actual tumors might be better.

GVAX can be patient specific, where cancer cells are taken specifically from each patient, genetically modified to secrete GM-CSF followed by irradiation and re-administered to the specific patient only. GVAX can also be non- patient-specific with the same types of cells used for all patients. Though the company has developed both patient-specific and non-patient –specific candidates, it has decided to focus on the latter.

Being a non-patient specific treatment makes production more reliable and cheaper, as the company does not have to deal with logistics such as getting each patient’s sample and shipping it back to the treatment facility on time. In addition, it is not always technically possible to generate a patient-specific GVAX cancer vaccine for every patient. Antigenics’ Oncophage® is a good example of a patient-specific cancer vaccine, as each patient undergoes surgery, to remove part or all of the cancerous tissue, followed by shipping of the tumor tissue to Antigenics’ manufacturing facility in Massachusetts. There, a specific antigen called heat shock protein gp96 is extracted from the tissue, re-sent to the medical center and administered to the patient. One must admit that although such a strategy may possess clinical benefits, this complicated procedure seems to be more expensive and to have more points of failure as oppose to an off-the–shelf treatment.

Although the trend in cancer therapy is clearly towards personalized therapy, an off-the-shelf product like GVAX is not necessarily therapeutically inferior to its patient-specific counterpart. In fact, it might have a significant advantage in the long run, considering the immune memory that can be created by cancer vaccines. Genetic instability is one of the hallmarks of cancer, as cancer cells constantly evolve by acquiring mutations and modifying exhibited antigens. These changes are a fundamental cause of treatment-resistance and disease recurrence, often demonstrated by cancer. A patient with early-stage disease who receives a cancer vaccine based on cells of advanced-stage disease could develop immunity against the advanced stages of the disease. Thus, non-personalized cancer vaccines have the potential of functioning as preventative treatments, blocking the formation of advanced-stage tumors. Such a preventative effect, which is still in the form of speculation, could be a huge differentiator for non-patient-specific cancer vaccines.

GM-CSF has been known as one of the most powerful immune stimulators. As such, it is often co-administered with cancer vaccines in order to stimulate the immune response. However, this co-administration is not targeted, as the GM-CSF is distributed throughout the patient’s body regardless of the vaccine location. Since GVAX cells constantly produce and secrete GM-CSF, even after being injected to the patient, there is always a local high GM-CSF concentration around them. Therefore, upon encountering antigen-presenting cells, the GVAX cells have better chances to induce a stronger immune stimulation than cancer vaccines which are simply co-administered with GM-CSF.

GVAX is being evaluated in multiple ongoing clinical trials for the treatment of prostate cancer, pancreatic cancer and Leukemia.

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