Abstract
Antibodies against autologous tumor-associated antigens have been demonstrated as being useful biomarkers for early cancer diagnosis and prognosis. They have several advantages such as long half-life (7–30 days depending on subtiter of Ig), inherent stability in patients’ blood due to not being subjected to proteolysis, well-studied biochemical properties, and their easy detections via secondary antibodies or antigens. Moreover, they can be easily screened in the serum using a noninvasive approach. Consequently, many technical approaches have been developed to study autoantibodies. We used serological proteome analysis (SERPA) for analyzing antibodies in pancreatic cancer patients’ sera, and the technique will be discussed in detail. SERPA has several advantages over other approaches currently used such as SEREX (serological analysis of tumor antigens by recombinant cDNA expression cloning) and phage display. SEREX involves the construction of a lambda phage cDNA library from tumor samples to infect bacteria. While library construction is a quite laborious and time-consuming procedure in SEREX, detection of posttranslational modifications that could be fundamental for antibody recognition is a major limitation of both SEREX and phage display techniques. SERPA avoids the time-consuming construction of cDNA libraries. In addition, since it does not rely on bacterial expression of antigens, antigens will have their usual posttranslational modifications preventing false-positive or -negative results in autoantibody profiling.
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References
Abadi ATB (2016) Vaccine against Helicobacter pylori: inevitable approach. World J Gastroenterol 22:3150–3157
Huh WK, Joura EA, Giuliano AR et al (2017) Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16–26 years: a randomised, double-blind trial. Lancet
Ridge JP, Di Rosa F, Matzinger P (1998) A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393:474–478
Schoenberger SP, Toes RE, van der Voort EI et al (1998) T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393:480–483
Mumberg D, Monach PA, Wanderling S et al (1999) CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-gamma. Proc Natl Acad Sci U S A 96:8633–8638
Qin Z, Blankenstein T (2000) CD4+ T cell—mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFN gamma receptor expression by nonhematopoietic cells. Immunity 12:677–686
Janssen EM, Lemmens EE, Wolfe T et al (2003) CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature 421:852–856
Jung S, Schluesener HJ (1991) Human T lymphocytes recognize a peptide of single point-mutated, oncogenic ras proteins. J Exp Med 173:273–276
Nakatsura T, Senju S, Ito M et al (2002) Cellular and humoral immune responses to a human pancreatic cancer antigen, coactosin-like protein, originally defined by the SEREX method. Eur J Immunol 32:826–836
Ramanathan RK, Lee KM, McKolanis J et al (2005) Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer. Cancer Immunol Immunother 54:254–264
Laheru D, Lutz E, Burke J et al (2008) Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res 14:1455–1463
Chaft JE, Litvak A, Arcila ME et al (2014) Phase II study of the GI-4000 KRAS vaccine after curative therapy in patients with stage I-III lung adenocarcinoma harboring a KRAS G12C, G12D, or G12V mutation. Clin Lung Cancer 15:405–410
Cappello P, Tomaino B, Chiarle R et al (2009) An integrated humoral and cellular response is elicited in pancreatic cancer by alpha-enolase, a novel pancreatic ductal adenocarcinoma-associated antigen. Int J Cancer 125:639–648
Capello M, Ferri-Borgogno S, Cappello P et al (2011) α-enolase: a promising therapeutic and diagnostic tumor target. FEBS J 278:1064–1074
Cappello P, Rolla S, Chiarle R et al (2013) Vaccination with ENO1 DNA prolongs survival of genetically engineered mice with pancreatic cancer. Gastroenterology 144:1098–1106
Kersten K, de Visser KE, van Miltenburg MH et al (2017) Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol Med 9:137–153
Jeong JH (2016) Inducible mouse models for cancer drug target validation. J Cancer Prev 21:243–248
Tan HT, Low J, Lim SG et al (2009) Serum autoantibodies as biomarkers for early cancer detection. FEBS J 276:6880–6904
Tomaino B, Cappello P, Capello M et al (2011) Circulating autoantibodies to phosphorylated α-enolase are a hallmark of pancreatic cancer. J Proteome Res 10:105–112
Tomaino B, Cappello P, Capello M et al (2007) Autoantibody signature in human ductal pancreatic adenocarcinoma. J Proteome Res 6:4025–4031
Capello M, Cappello P, Linty FC et al (2013) Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models. J Hematol Oncol 6:67
Griggio V, Mandili G, Vitale C et al (2016) Humoral immune responses toward tumor-derived antigens in previously untreated patients with chronic lymphocytic leukemia. Oncotarget 8:3274–3288
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Cappello, P., Bulfamante, S., Mandili, G., Novelli, F. (2022). Discovery of Targets for Cancer Immunoprevention. In: McAllister, F. (eds) Cancer Immunoprevention. Methods in Molecular Biology, vol 2435. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2014-4_3
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DOI: https://doi.org/10.1007/978-1-0716-2014-4_3
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