Cancer vaccine

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The term cancer vaccine is often used to describe a process whereby a person's immune system is coaxed into recognizing and destroying malignant cells without harming normal cells. A cancer vaccine is generally considered an immunotherapy, because, unlike prophylactic vaccines against diseases such as polio, influenza, and tuberculosis, a cancer vaccine is not preventive and must be administered after cancerous cells develop. Note that the HPV vaccine and the Hepatitis B vaccine are not cancer vaccines as described above. It works by preventing infection by the HPV thereby reducing the occurrence of cervical cancer, not by coaxing the body into recognizing and destroying malignant cells.

Problems

A vaccine against a particular virus is relatively easy to create. The virus is foreign to the body, and therefore will express antigens, which 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, the most suitable stage for a cancer vaccine is likely to be minimal residual disease)

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).

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 Genitope Corp (MyVax personalized immunotherapy), Onyvax Limited[2] (Onyvax-P), Antigenics Inc. (Oncophage), Geron Corporation (GRNVAC1), Favrille Inc (FavId), 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.[3] (NeuVax).

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