Circulating Autoantibodies to Phosphorylated α-Enolase are a Hallmark of Pancreatic Cancer

Tomaino, Barbara; Cappello, Paola; Capello, Michela; Fredolini, Claudia; Sperduti, Isabella; Migliorini, Paola; Salacone, Paola; Novarino, Anna; Giacobino, Alice; Ciuffreda, Libero; Alessio, Massimo; Nisticò, Paola; Scarpa, Aldo; Pederzoli, Paolo; Zhou, Weidong; Petricoin, Emanuel F.; Liotta, Lance A.; Giovarelli, Mirella; Milella, Michèle; Novelli, Francesco

doi:10.1021/pr100213b

Cited by 108 publications

(123 citation statements)

References 35 publications

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“…Auto-Abs are highly specific, stable, and handily detectable in small volumes of specimens with well-established secondary reagents. These advantages lead many efforts into discovery of auto-Abs as biomarkers for detection of various types of cancers, such as colorectal (10)(11)(12), breast (13)(14)(15), ovarian (16,17), lung (18)(19)(20), liver (21,22), and pancreatic (23,24) cancers. As for OSCC, five auto-Abs have been individually identified as serum biomarker candidates, including anti-p53 (25)(26)(27)(28), anti-survivin (29,30), anticytokeratin 8 (CK-8; ref.…”

Section: Introductionmentioning

confidence: 99%

Salivary Auto-Antibodies as Noninvasive Diagnostic Markers of Oral Cavity Squamous Cell Carcinoma

Chang

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Oral cavity squamous cell carcinoma (OSCC) is one of the most common cancers worldwide, and its incidence is still increasing. Approximately 50% of patients with OSCC die within 5 years after diagnosis, mostly ascribed to the fact that the majority of patients present advanced stages of OSCC at the time of diagnosis.Methods: To discover salivary biomarkers for ameliorating the detection of OSCC, herein, we developed a multiplexed bead-based platform to simultaneously detect auto-antibodies (auto-Abs) in salivary samples.Results: Compared with healthy individuals, the salivary levels of anti-p53, anti-survivin, anti-Hsp60, and anti-RPLP0 were significantly elevated in patients with OSCC. Noteworthily, the elevated levels of anti-p53, anti-survivin, and anti-Hsp60 were already observed in individuals with oral potentially malignant disorder. Moreover, the salivary levels of anti-p53, anti-survivin, anti-Hsp60, anti-RPLP0, and anti-CK8 were significantly elevated in patients with early-stage OSCC compared with those in healthy individuals. Most importantly, the use of a combined panel of salivary anti-p53, anti-survivin, anti-Hsp60, and anti-RPLP0 largely improves the detection of OSCC.Conclusion: Collectively, our results reveal that the salivary auto-Abs are effective OSCC biomarkers and the four-auto-Ab panel provides a novel and practicable approach for OSCC screening.Impact: This study provides the first evidence for the potential clinical application of salivary auto-Abs in OSCC diagnosis. Cancer Epidemiol Biomarkers Prev; 23(8); 1569-78. Ó2014 AACR.

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Section: Introductionmentioning

confidence: 99%

Salivary Auto-Antibodies as Noninvasive Diagnostic Markers of Oral Cavity Squamous Cell Carcinoma

Chang

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…3 One of these antigens, ␣-enolase (ENO1), is specifically recognized by more than 60% of patients with PDA. 4 ENO1 is coded by the ENO1 gene, is overexpressed in the cytoplasm of PDA cells, and is also present on their membrane. 5 In the cytoplasm, ENO1 acts as a glycolytic enzyme, whereas on the membrane it acts as a plasminogen receptor and plays an important role in cell migration.…”

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confidence: 99%

Vaccination With ENO1 DNA Prolongs Survival of Genetically Engineered Mice With Pancreatic Cancer

et al. 2013

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See Covering the Cover synopsis on page 862. BACKGROUND & AIMS:Pancreatic ductal adenocarcinoma (PDA) is an aggressive tumor, and patients typically present with late-stage disease; rates of 5-year survival after pancreaticoduodenectomy are low. Antibodies against ␣-enolase (ENO1), a glycolytic enzyme, are detected in more than 60% of patients with PDA, and ENO1-specific T cells inhibit the growth of human pancreatic xenograft tumors in mice. We investigated whether an ENO1 DNA vaccine elicits antitumor immune responses and prolongs survival of mice that spontaneously develop autochthonous, lethal pancreatic carcinomas. METHODS:We injected and electroporated a plasmid encoding ENO1 (or a control plasmid) into Kras G12D /Cre (KC) mice and Kras G12D /Trp53 R172H /Cre (KPC) mice at 4 weeks of age (when pancreatic intraepithelial lesions are histologically evident). Antitumor humoral and cellular responses were analyzed by histology, immunohistochemistry, enzyme-linked immunosorbent assays, flow cytometry, and enzyme-linked immunosorbent spot and cytotoxicity assays. Survival was analyzed by Kaplan-Meier analysis. RESULTS: The ENO1 vaccine induced antibody and a cellular response and increased survival times by a median of 138 days in KC mice and 42 days in KPC mice compared with mice given the control vector. On histologic analysis, the vaccine appeared to slow tumor progression. The vaccinated mice had increased serum levels of anti-ENO1 immunoglobulin G, which bound the surface of carcinoma cells and induced complement-dependent cytotoxicity. ENO1 vaccination reduced numbers of myeloid-derived suppressor cells and T-regulatory cells and increased T-helper 1 and 17 responses. CONCLU-SIONS: In a genetic model of pancreatic carcinoma, vaccination with ENO1 DNA elicits humoral and cellular immune responses against tumors, delays tumor progression, and significantly extends survival. This vaccination strategy might be developed as a neoadjuvant therapy for patients with PDA.

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“…Among these, ENO1 has been shown to be a promising candidate target as it was recognized by the autoantibodies present in .60% of patients with PDA. 26,104 ENO1 is coded by the ENO1 gene and is overexpressed in the cytoplasm of PDA cells being For complete review see ClinicalTrials.gov. Abbreviations: PDA, pancreatic ductal adenocarcinoma; GM-CSF, granulocyte and monocyte-colony stimulating factor; FOLFiRiNOX, 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin; NS, not specified; VEGF-R, vascular endothelial growth factor-receptor; KLH, keyhole limphet hemocyanin.…”

Section: Passive Immunotherapy Combined With Antitumor Vaccinesmentioning

confidence: 99%

“…These autoantibodies recognize the cytoskeletal protein Ezrin 25 and the phosphorylated α-enolase (ENO1), a glycolytic enzyme, which also functions as a plasminogen receptor. 26 Combined detection of antibodies to Ezrin, phosphorylated ENO1, and CA 19-9 correctly discriminates PDA from control patients with high sensitivity and specificity. 25 A cell surface proteoglycan, glypican-1, specifically enriched on PDA cell-derived exosomes, was found to be able to discriminate early stages of pancreatic cancer.…”

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confidence: 99%

Pancreatic cancer vaccine: a unique potential therapy

Cappello¹,

Principe²,

Novelli³

2015

GICTT

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Pancreatic ductal adenocarcinoma (PDA) is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological checkpoints. Keywords: pancreatic cancer, vaccines, T-cells, antibody, immunotherapy Pancreatic cancerAlthough lung, breast, prostate, and colorectal cancers are considered to be the "big four" cancer types in the USA, pancreas and liver cancers are expected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related deaths by 2030, respectively.1 Pancreatic ductal adenocarcinomas (PDAs) arise from the exocrine pancreas and account for 95% of pancreatic cancers. In the USA, there were an estimated 48,960 cases of new-onset pancreatic cancer in 2015, which led to 40,560 deaths, with a 5-year survival rate of ∼7%.3 PDA is nearly universally lethal; ,20% of patients are suitable candidates for surgery at the time of diagnosis, and the median survival rate is 3.5 months and 12.6 months for nonresected patients and resected patients, respectively.2,4 PDA evolves from noninvasive precursor lesions that do not invade the basement membrane. [5][6][7] Three precursors have been characterized, namely, pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms, and mucinous cystic neoplasms.

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Circulating Autoantibodies to Phosphorylated α-Enolase are a Hallmark of Pancreatic Cancer

Abstract: This is an author version of the contribution published on:Questa è la versione dell'autore dell'opera: J Proteome Res. 2011 Jan 7;10(1):105-12. doi: 10.1021

Cited by 108 publications

References 35 publications

Salivary Auto-Antibodies as Noninvasive Diagnostic Markers of Oral Cavity Squamous Cell Carcinoma

Salivary Auto-Antibodies as Noninvasive Diagnostic Markers of Oral Cavity Squamous Cell Carcinoma

Vaccination With ENO1 DNA Prolongs Survival of Genetically Engineered Mice With Pancreatic Cancer

Pancreatic cancer vaccine: a unique potential therapy

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