Tumour Antigens Recognised by Antibodies

Abstract

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.
close

References

Bei R , Masuelli L , Palumbo C , Modesti M and Modesti A (2009) A common repertoire of autoantibodies is shared by cancer and autoimmune disease patients: Inflammation in their induction and impact on tumor growth. Cancer Letters 281 (1): 8–23.

Bright RK , Bright JD and Byrne JA (2014) Overexpressed oncogenic tumor‐self antigens. Human Vaccines & Immunotherapeutics 10 (11): 3297–3305.

Burtin P , von Kleist S , Rapp W , et al. (1965) Autoantibodies in cancer patients. La Presse Médicale 73 (46): 2599–2603.

Casiano CA , Mediavilla‐Varela M and Tan EM (2006) Tumor‐associated antigen arrays for the serological diagnosis of cancer. Molecular & Cellular Proteomics 5 (10): 1745–1759.

Chen YT (2004) Identification of human tumor antigens by serological expression cloning: an online review on SEREX. Cancer Immunity, http://www.cancerimmunity.org/serex.

Chen YT , Gure AO and Scanlan MJ (2005) Serological analysis of expression cDNA libraries (SEREX): an immunoscreening technique for identifying immunogenic tumor antigens. Methods in Molecular Medicine 103: 207–216.

Cramer DW , Bast RC Jr , Berg CD , et al. (2011) Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prevention Research (Philadelphia, Pa.) 4 (3): 365–374.

de Visser KE , Eichten A and Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nature Reviews Cancer 6 (1): 24–37.

Ehrlich JR , Tang L , Caiazzo RJ Jr , et al. (2008) The ‘reverse capture’ autoantibody microarray : an innovative approach to profiling the autoantibody response to tissue‐derived native antigens. Methods in Molecular Biology 441: 175–192.

Erkanli A , Taylor DD , Dean D , et al. (2006) Application of Bayesian modeling of autologous antibody responses against ovarian tumor‐associated antigens to cancer detection. Cancer Research 66 (3): 1792–1798.

Gnjatic S , Old LJ and Chen YT (2009) Autoantibodies against cancer antigens. Methods in Molecular Biology 520: 11–19.

Gnjatic S , Ritter E , Buchler MW , et al. (2010) Seromic profiling of ovarian and pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America 107 (11): 5088–5093.

Hellstrom I , Raycraft J , Kanan S , et al. (2006) Mesothelin variant 1 is released from tumor cells as a diagnostic marker. Cancer Epidemiology, Biomarkers & Prevention 15 (5): 1014–1020.

Luborsky JL , Yu Y , Edassery SL , et al. (2011) Autoantibodies to mesothelin in infertility. Cancer Epidemiology, Biomarkers & Prevention 20 (9): 1970–1978.

Pastan I and Hassan R (2014) Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Research 74 (11): 2907–2912.

Ragupathi G , Liu NX , Musselli C , et al. (2005) Antibodies against tumor cell glycolipids and proteins, but not mucins, mediate complement‐dependent cytotoxicity. Journal of Immunology 174 (9): 5706–5712.

Reuschenbach M , von Knebel Doeberitz M and Wentzensen N (2009) A systematic review of humoral immune responses against tumor antigens. Cancer Immunology, Immunotherapy 58 (10): 1535–1544.

Ritter G and Livingston PO (1991) Ganglioside antigens expressed by human cancer cells. Seminars in Cancer Biology 2 (6): 401–409.

Sahin U , Tureci O , Schmitt H , et al. (1995) Human neoplasms elicit multiple specific immune responses in the autologous host. Proceedings of the National Academy of Sciences of the United States of America 92 (25): 11810–11813.

Scott AM , Allison JP and Wolchok JD (2012) Monoclonal antibodies in cancer therapy. Cancer Immunity 12: 14.

Soussi T (2000) p53 Antibodies in the sera of patients with various types of cancer: a review. Cancer Research 60 (7): 1777–1788.

Stockert E , Jager E , Chen YT , et al. (1998) A survey of the humoral immune response of cancer patients to a panel of human tumor antigens. Journal of Experimental Medicine 187 (8): 1349–1354.

Wandall HH , Blixt O , Tarp MA , et al. (2010) Cancer biomarkers defined by autoantibody signatures to aberrant O‐glycopeptide epitopes. Cancer Research 70 (4): 1306–1313.

Zhang JY , Looi KS and Tan EM (2009) Identification of tumor‐associated antigens as diagnostic and predictive biomarkers in cancer. Methods in Molecular Biology 520: 1–10.

Zola H (2006) Medical applications of leukocyte surface molecules – the CD molecules. Molecular Medicine 12 (11‐12): 312–316.

Further Reading

Adams GP and Weiner LM (2005) Monoclonal antibody therapy of cancer. Nature Biotechnology 23 (9): 1147–1157.

Conrad K and Kupper J (2014) Tumor‐Associated Autoantibodies. In: Schoenfeld Y , Meroni PL and Gershwin ME (eds) Autoantibodies, 3rd edn, chap. 33, pp. 275–289. Boston: Elsevier http://booksite.elsevier.com/9780444563781.

Polanski M and Anderson NL (2007) A list of candidate cancer biomarkers for targeted proteomics. Biomarker Insights 1: 1–48.

Scott AM , Wolchok JD and Old LJ (2012) Antibody therapy of cancer. Nature Reviews Cancer 12 (4): 278–87.

Zaenker P and Ziman MR (2013) Serologic autoantibodies as diagnostic cancer biomarkers – a review. Cancer Epidemiology, Biomarkers and Prevention 22 (12): 2161–2181.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
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]