Tumour Antigens Recognised by Antibodies


Humoral and cellular immune responses to tumour antigens occur during tumourigenesis. Since 1965, there has been an ongoing search for cancer‐specific antibodies as these have potential applications as specific diagnostic and therapeutic tools. Serum antibodies from cancer patients have been used to identify hundreds of tumour antigens. Owing to the biochemical heterogeneity of tumours, even of the same type, each patient has a slightly different repertoire of autoantibodies. However, there is an overall characteristic polyclonal signature for specific tumour types. Thus, multi‐antigen assays to detect cancer signatures are in development as diagnostic tests. For antigen‐targeted therapy, monoclonal antibodies to individual antigens have been produced and some are FDA approved for cancer treatment.

Key Concepts

  • Autoantibodies against aberrant or overexpressed tumour antigens are induced during tumour development.
  • Tumour‐associated autoantibodies have potential for cancer diagnosis and prognosis.
  • Individual autoantibodies have a relatively low sensitivity while multiplex antigen arrays that detect multiple autoantibodies provide a higher specificity and sensitivity for tumour detection.
  • Serum autoantibodies have been useful in identifying tumour antigens that can be used to characterise tumours and as therapeutic targets.
  • Monoclonal antibodies against specific tumour antigens can be produced in the laboratory.
  • Multiple monoclonal antibodies produced against cancer‐specific antigens have been FDA approved for cancer therapy.

Keywords: tumour; antigen; antitumour antibodies; polyclonal; monoclonal

Figure 1. Comparison of major features of polyclonal and monoclonal antibodies.
Figure 2. SEREX uses the antibody repertoire of cancer patients to define highly immunoreactive tumour antigens. A cDNA expression library is constructed from a tumour specimen, and cloned into phage expression vectors and the resulting recombinant phage are used to transfect Escherichia coli. The resulting recombinant proteins are transferred onto nitrocellulose membranes, and incubated with diluted serum from the autologous patient. Clones reactive with high‐titre antibodies are identified with an enzyme‐conjugated secondary antibody against human IgG. For positive clones, the nucleotide sequence of the cDNA insert is determined. This sequence is used to search databases. Tumour antigens corresponding to the cDNA sequence found in the databases are identified.
Figure 3. An example of multiple antibodies to selected antigens in ovarian cancer patients and patients with early ovarian failure who may be a risk group for ovarian cancer. Antibodies were detected in sera (1:100) in immunoassays using recombinant protein. (a) Antibodies to selected individual proteins (abbreviations: GAPDH, glyceraldehyde phosphate dehydrogenase; PDIA3, protein disulphide isomerase family A; SBP1, selenium binding protein 1; ALDH, aldehyde dehydrogenases 1A1 and 3A1). Enolase is a common background autoantibody in healthy individuals; it was the only antibody to the antigen panel found in control sera. (b) The data in ‘A’ was rearranged to show the total frequency of antibody reactions in each sera.


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Further Reading

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Luborsky, Judith(Aug 2015) Tumour Antigens Recognised by Antibodies. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001433.pub2]