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Tumor antigen



Tumor antigen is a substance produced in tumor cells that triggers an immune response in the host. Tumor antigens are useful in identifying tumor cells and are potential candidates for use in cancer therapy.

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Contents

Mechanism of tumor antigenesis

Normal proteins in the body are not antigenic because of self-tolerance, a process in which self-reacting cytotoxic T lymphocytes (CTLs) and autoantibody-producing B lymphocytes are culled in the thymus. Thus any protein that is not exposed to the immune system triggers an immune response. This may include normal proteins that are well sequestered from the immune system, proteins that are normally produced in extremely small quantities, proteins that are normally produced only in certain stages of development, or proteins whose structure is modified due to mutation.

Types

Any protein produced in a a tumor cell that has an abnormal structure due to mutation can act as a tumor antigen. Such abnormal proteins are produced due to mutation of the concerned gene. Mutation of protooncogenes and tumor suppressors which lead to abnormal protein production are the cause of the tumor and thus such abnormal proteins are called tumor-specific antigens. Examples of tumor-specific antigens include the abnormal products of ras and p53 genes. In contrast, mutation of other genes unrelated to the tumor formation may lead to synthesis of abnormal proteins which are called tumor-associated antigens.

Proteins that are normally produced in very low quantities but whose production is dramatically increased in tumor cells, trigger an immune response. An example of such a protein is the enzyme tyrosinase, which is required for melanin production. Normally tyrosinase is produced in minute quantities but its levels are very much elevated in melanoma cells.

Oncofetal antigens are another important class of tumor antigens. Examples are alphafetoprotein (AFP) and carcinoembryonic antigen (CEA). These proteins are normally produced in the early stages of embryonic development and disappear by the time the immune system is fully developed. Thus self-tolerance does not develop against these antigens.

Abnormal proteins are also produced by cells infected with oncoviruses, eg. EBV and HPV. Cells infected by these viruses contain latent viral DNA which is transcribed and the resulting protein produces an immune response.

In addition to proteins, other substances like cell surface glycolipids and glycoproteins may also have an abnormal structure in tumor cells and could thus be targets of the immune system.

Importance of tumor antigens

Tumor antigens, because of their relative abundance in tumor cells are useful in identifying specific tumor cells. Certain tumors have certain tumor antigens in abundance.

Tumor antigen Tumor in which it is found Remarks
Alphafetoprotein (AFP) Germ cell tumors
Carcinoembryonic antigen (CEA)
CA-125 Ovarian cancer
MUC-1 breast cancer
epithelial tumor antigen (ETA) breast cancer
Tyrosinase malignant melanoma normally present in minute quantities; greatly elevated levels in melanoma
Melanoma-associated antigen (MAGE) malignant melanoma Also normally present in the testis
abnormal products of ras, p53 Various tumors

Certain tumor antigens are thus used as tumor markers. More importantly, tumor antigens can be used in cancer therapy as tumor antigen vaccines. [1]

See also

References

  1. ^ M Hareuveni, C Gautier, M Kieny, D Wreschner, P Chambon and R Lathe; Vaccination Against Tumor Cells Expressing Breast Cancer Epithelial Tumor Antigen; Proceedings of the National Academy of Sciences, Vol 87, 9498-9502, 1990.
  • Kumar, Abbas, Fausto; Robbins and Cotran: Pathologic Basis of Disease; Elsevier, 7th ed.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Tumor_antigen". A list of authors is available in Wikipedia.
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