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Identification of tumor antigens for clinical evaluation 

Identification of tumor antigens for clinical evaluation
Chapter:
Identification of tumor antigens for clinical evaluation
Author(s):

Jayakumar Vadakekolathu

, Amanda K Miles

, David J Boocock

, and Stephanie EB McArdle

DOI:
10.1093/med/9780199676866.003.0009
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date: 25 June 2022

The idea of the immune system being able to fight cancerous cells was first put forward during the 18th century when German doctors observed that infected tumors would often shrink dramatically. William Coley (1862–1936), treated patients with cancer in a large scale with a Streptococcus pyogenes preparation, later nicknamed ‘Coley’s toxin’. In 1909 Metchnikoff and Ehrlich hypothesized that the immune system suppresses the growth of tumors, which gave rise to the concept of ‘immunosurveillance’ in 1967 by Burnet who proposed that lymphocytes play a central role in the detection and rejection of transformed malignant cells in the human body. What the immune system recognized, however, remained undiscovered for 34 years and the real breakthrough, came with the identification and cloning of the first tumor-specific antigen called MAGE-1 (a melanoma tumor antigen), which stimulates cytotoxic T lymphocytes (CTLs), by Van der Bruggen in 1991. They demonstrated for the first time the actual existence of a protein expressed by tumor cells that could induce a T-cell immune response in humans and this revitalized immunotherapy, opening up novel strategies to target tumors by evoking T-cell mediated immunity following vaccination. Since then the identification and characterization of proteins preferentially expressed by cancer cells (so-called cancer antigens) became vital for the understanding and monitoring of the disease as well as for the identification of potential targets for either immune or drug therapy. The chapter discusses the various historic and current techniques used to discover tumor antigens for clinical evaluation.

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