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The term cancer vaccine refers to a vaccine that either prevents infections with cancer-causing viruses, or treats existing cancer.
Some cancers, such as cervical cancer and some liver cancers, are caused by viruses, and traditional vaccines against those viruses, such as HPV vaccine and Hepatitis B vaccine, will prevent those cancers.
Scientists have also been trying to develop vaccines against existing cancers. Some researchers believe that cancer cells routinely arise and are destroyed by the healthy immune system; cancer forms when the immune system fails to destroy them. They are separating proteins from cancer cells and immunizing cancer patients against those proteins, in the hope of stimulating an immune reaction that would kill the cancer cells. Therapeutic cancer vaccines are being developed for the treatment of breast, lung, colon, skin, kidney, prostate, and other cancers.[1] But they have not yet been proven to work in phase 3 human trials, and have not been approved by the U.S. Food and Drug Administration or by European Union regulatory agencies.[2]
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Problems
A vaccine against a particular virus is relatively easy to create. The virus is foreign to the body, and therefore will express antigens the immune system can recognize. Furthermore, there are usually only a few viable variants of the virus in question. It is very hard to develop vaccines for viruses that mutate constantly such as influenza or HIV.
A tumour can have many different types of cells in it, each with different cell-surface antigens. Furthermore, those cells are derived from the individual with cancer, and therefore display few if any antigens that are foreign to that individual. This makes it difficult for the immune system to distinguish the cancer cells from normal cells. Renal cancer and melanoma are the two cancers with most evidence of causing spontaneous and effective immune responses, possibly because they often display antigens that are recognized as foreign. Therefore, many attempts at developing cancer vaccines are directed against these tumors.
However, most clinical trials investigating a cancer vaccine against melanoma and renal cancer have failed. The precise reasons are unknown, but possible explanations include:
1) disease stage being treated was too advanced: it is difficult to get the immune system to fight bulky tumor deposits, because tumors actively suppress the immune system using a variety of mechanisms (e.g. secretion of cytokines that inhibit immune activity). The most suitable stage for a cancer vaccine is likely to be early disease, when the tumor volume is low, but the problem there is that clinical trials take upwards of five years and require high numbers of patients to reach measurable end points. The alternative is to target patients with minimal residual disease after de-bulking of the tumor by surgery, radiotherapy or (providing it does not in itself harm the immune system) chemotherapy.
2) escape loss variants (cancer vaccines that target just one tumor antigen are likely to be less effective. Tumors are highly heterogeneous and antigen expression differs markedly between tumors (even within deposits in the same patient). The most effective cancer vaccine is likely to raise an immune response against a broad range of tumor antigens to minimise the chance of the tumor being able to mutate and become resistant to the therapy.)
3) prior treatments (numerous clinical trials in the past have treated patients who have received numerous cycles of chemotherapy. Chemotherapy is often myelosuppressive and destroys the immune system. There is little point giving a cancer vaccine to a patient who is immune suppressed).
4) some tumors progress very rapidly and/or unpredictably, and they can literally outpace the immune system. It may take two to three months for an immune response to a vaccine to mature, but some cancers (e.g. advanced pancreatic) can produce marked clinical deterioration, or even death, within this timeframe.
5) many cancer vaccine clinical trials examine immune responses by patients as their primary goal. Correlations are then made, typically showing that the patients who made the strongest immune responses were the ones who lived the longest, and this is taken as evidence that the vaccine is working. The alternative explanation, however, is that the patients who made the best immune responses were the healthier patients with the better prognosis, and they would have survived longest in any event, even without the vaccine. In other words, the immune responses may simply be a simple reflection of a better health status, not an indication that the vaccine had any beneficial effects. As such, these immune 'false friends' may have tempted some to embark on expensive phase III trials without a solid rationale.
Drug Development
Most of the cancer vaccines in development are addressing specific cancer types and are therapeutic vaccines. Several cancer vaccines are currently in development by companies such as Antigenics Inc. (Oncophage), Pharmexxa A/S (GV1001), Onyvax Limited[1] (Onyvax-P), Geron Corporation (GRNVAC1), Dendreon Corp (Provenge), Cell Genesys Inc (GVAX),Advaxis, Inc (Lovaxin C), Accentia Biopharmaceuticals majority owned subsidiary Biovest International [BiovaxID], GeneMax Corp (GMXX) and Apthera, Inc.[2] (NeuVax).
CancerVax (Canvaxin), Genitope Corp (MyVax personalized immunotherapy), Favrille Inc (FavId), Therion (Panvac) are examples of cancer vaccine projects that have been terminated due to poor phase III results (despite promising phase II data and strong immune responses).
On April 8 2008, New York-based company Antigenics announced that it had received approval for the first therapeutic cancer vaccine in Russia. It is the first approval by a regulatory body of a cancer immunotherapy. The treatment, Oncophage, increased recurrence-free survival by a little more than a year according to the results of a phase III clinical trial. It awaits approval in the US and EU.[3]
References
- ^ Giarelli E (2007). "Cancer vaccines: a new frontier in prevention and treatment". Oncology (Williston Park) 21 (11 Suppl Nurse Ed): 11–8. PMID 18154203.
- ^ National Cancer Institute, Cancer Vaccine Fact Sheet, Updated: 06/08/2006
- ^ The Scientist : NewsBlog : 1st cancer vaccine approved in Russia [9th April 2008]
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- This page was last modified on 2 October 2008, at 08:43.
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