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Microbiology and Immunology 2003A novel cancer vaccine consisting of fixed autologous cancer tissue-fragments, microparticles encapsulating cytokines, and an adjuvant was developed. In a Phase I/IIa... (Review)
Review
A novel cancer vaccine consisting of fixed autologous cancer tissue-fragments, microparticles encapsulating cytokines, and an adjuvant was developed. In a Phase I/IIa clinical trial, vaccination to patients after resection of hepatocellular carcinoma induced significantly longer time before the first recurrence than that in historical control patients operated in the same department (P < 0.05). This formulation will be promising against recurrence of many types of human cancers.
Topics: BCG Vaccine; Cancer Vaccines; Carcinoembryonic Antigen; Combined Modality Therapy; Humans; Male; Melanoma; Middle Aged; Models, Biological; Neoplasm Recurrence, Local; Neoplasms; T-Lymphocytes, Cytotoxic
PubMed: 12801062
DOI: 10.1111/j.1348-0421.2003.tb03393.x -
Medical Science Monitor : International... Jul 2017BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T...
Combined Blockade of T Cell Immunoglobulin and Mucin Domain 3 and Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Results in Durable Therapeutic Efficacy in Mice with Intracranial Gliomas.
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1. The CD4+, CD8+, and regulatory T cells in brain-infiltrating lymphocytes were analyzed using flow cytometry, and the effector function of T cells was assessed using ELISA. We performed a rechallenge by subcutaneous injection of GL261 cells in the "cured" (>90 days post-orthotopic tumor implantation) and naïve mice. RESULTS The mean survival time in the control, anti-Tim-3, anti-CEACAM1, and combined treatment groups was 29.8, 43.4, 42.3, and 86.0 days, respectively, with 80% of the mice in the combined group becoming long-term survivors showing immune memory against glioma cells. Infiltrating CD4+ and CD8+ T cells increased and immunosuppressive Tregs decreased with the combined therapy, which resulted in a markedly elevated ratio of CD4+ and CD8+ cells to Tregs. Additionally, plasma IFN-γ and TGF-β levels were upregulated and downregulated, respectively. CONCLUSIONS Our data indicate that combined blockade of Tim-3 and CEACAM1 generates robust therapeutic efficacy in mice with intracranial tumors, and provides a promising option for GBM immunotherapy.
Topics: Animals; Antibodies, Monoclonal; Antilymphocyte Serum; Brain Neoplasms; CD8-Positive T-Lymphocytes; Carcinoembryonic Antigen; Disease Models, Animal; Glioblastoma; Glioma; Hepatitis A Virus Cellular Receptor 2; Immune Tolerance; Immunotherapy; Mice; Mice, Inbred C57BL; Receptors, Virus; Transforming Growth Factor beta; Treatment Outcome
PubMed: 28736431
DOI: 10.12659/msm.903098 -
The Journal of Thoracic and... May 2019
Topics: Carcinoembryonic Antigen; Colorectal Neoplasms; Humans; Liver Neoplasms; Metastasectomy; Prognosis
PubMed: 30827535
DOI: 10.1016/j.jtcvs.2019.01.016 -
Arquivos de Gastroenterologia 2022The role of ascitic and serum levels of various tumour biomarkers in the discrimination of cause of ascites is not well established.
BACKGROUND
The role of ascitic and serum levels of various tumour biomarkers in the discrimination of cause of ascites is not well established.
OBJECTIVE
To evaluate the role of serum and ascitic levels of tumor biomarkers (CA 72-4, CA 19-9, CEA and CA 125) in discrimination of cause of ascites.
METHODS
A prospective study was conducted in consecutive patients presenting with ascites. Serum and ascitic levels of CA 19-9, CA 125, CA 72-4 and carcinoembryonic antigen (CEA) were determined at the presentation. The patients with cirrhotic ascites, tuberculous peritonitis (TBP) and peritoneal carcinomatosis (PC) were eventually included in analysis.
RESULTS
Of the 93 patients (58 males, mean age 47 years) included, the underlying cause was cirrhosis in 31, PC in 42 and peritoneal tuberculosis in 20. The best cutoff for discriminating benign and malignant ascites for serum CEA, CA 19-9 and CA 72-4 were 6.7 ng/mL, 108 IU/mL and 8.9 IU/mL, respectively. The best cutoff for discriminating benign and malignant ascites for ascitic CA 125, CEA, CA 19-9 and CA 72-4 were 623 IU/mL, 8.7 ng/mL, 33.2 IU/mL and 7 IU/mL, respectively.
CONCLUSION
The performance of single biomarker for the prediction of underlying PC is low but a combination of serum CA 19-9 and CA 72-4 best predicted the presence of peritoneal carcinomatosis.
Topics: Ascites; Ascitic Fluid; Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Humans; Male; Middle Aged; Peritoneal Neoplasms; Prospective Studies
PubMed: 35830029
DOI: 10.1590/S0004-2803.202202000-37 -
Molecular & Cellular Proteomics : MCP Nov 2023Carcinoembryonic antigen (CEA) of human plasma is a biomarker of many cancer diseases, and its N-glycosylation accounts for 60% of molecular mass. It is highly desirable...
Carcinoembryonic antigen (CEA) of human plasma is a biomarker of many cancer diseases, and its N-glycosylation accounts for 60% of molecular mass. It is highly desirable to characterize its glycoforms for providing additional dimension of features to increase its performance in prognosis and diagnosis of cancers. However, to systematically characterize its site-specific glycosylation is challenging because of its low abundance. Here, we developed a highly sensitive strategy for in-depth glycosylation profiling of plasma CEA through chemical proteomics combined with multienzymatic digestion. A trifunctional probe was utilized to generate covalent bond of plasma CEA and its antibody upon UV irradiation. As low as 1 ng/ml CEA in plasma could be captured and digested with trypsin and chymotrypsin for intact glycopeptide characterization. Twenty six of 28 potential N-glycosylation sites were well identified, which were the most comprehensive N-glycosylation site characterization of CEA on intact glycopeptide level as far as we known. Importantly, this strategy was applied to the glycosylation analysis of plasma CEA in cancer patients. Differential site-specific glycoforms of plasma CEA were observed in patients with colorectal cancers (CRCs) and lung cancer. The distributions of site-specific glycoforms were different as the progression of CRC, and most site-specific glycoforms were overexpressed in stage II of CRC. Overall, we established a highly sensitive chemical proteomic method to profile site-specific glycosylation of plasma CEA, which should generally applicable to other well-established cancer glycoprotein biomarkers for improving their cancer diagnosis and monitoring performance.
Topics: Humans; Glycosylation; Carcinoembryonic Antigen; Proteomics; Biomarkers, Tumor; Glycopeptides; Lung Neoplasms
PubMed: 37820924
DOI: 10.1016/j.mcpro.2023.100662 -
Cell Jun 2018Macrophages protect the body from damage and disease by targeting antibody-opsonized cells for phagocytosis. Though antibodies can be raised against antigens with...
Macrophages protect the body from damage and disease by targeting antibody-opsonized cells for phagocytosis. Though antibodies can be raised against antigens with diverse structures, shapes, and sizes, it is unclear why some are more effective at triggering immune responses than others. Here, we define an antigen height threshold that regulates phagocytosis of both engineered and cancer-specific antigens by macrophages. Using a reconstituted model of antibody-opsonized target cells, we find that phagocytosis is dramatically impaired for antigens that position antibodies >10 nm from the target surface. Decreasing antigen height drives segregation of antibody-bound Fc receptors from the inhibitory phosphatase CD45 in an integrin-independent manner, triggering Fc receptor phosphorylation and promoting phagocytosis. Our work shows that close contact between macrophage and target is a requirement for efficient phagocytosis, suggesting that therapeutic antibodies should target short antigens in order to trigger Fc receptor activation through size-dependent physical segregation.
Topics: Animals; Antibodies, Monoclonal; Antigens; Carcinoembryonic Antigen; Gene Editing; Integrins; Leukocyte Common Antigens; Macrophages; Mice; Opsonin Proteins; Phagocytosis; Phosphorylation; RAW 264.7 Cells; Receptors, Fc; Unilamellar Liposomes
PubMed: 29958103
DOI: 10.1016/j.cell.2018.05.059 -
Mutation Research Aug 2005In recent years, investigators have carried out several studies designed to evaluate whether human tumor-associated antigens might be exploited as targets for active... (Review)
Review
In recent years, investigators have carried out several studies designed to evaluate whether human tumor-associated antigens might be exploited as targets for active specific immunotherapy, specifically human cancer vaccines. Not too long ago such an approach would have been met with considerable skepticism because the immune system was believed to be a rigid discriminator between self and non-self which, in turn, protected the host from a variety of pathogens. That viewpoint has been challenged in recent years by a series of studies indicating that antigenic determinants of self have not induced absolute host immune tolerance. Moreover, under specific conditions that evoke danger signals, peptides from self-antigen can be processed by the antigen-presenting cellular machinery, loaded onto the major histocompatibility antigen groove to serve as targets for immune intervention. Those findings provide the rationale to investigate a wide range of tumor-associated antigens, including differentiation antigens, oncogenes, and tumor suppressor genes as possible immune-based targets. One of those tumor-associated antigens is the carcinoembryonic antigen (CEA). Described almost 40 years ago, CEA is a M(r) 180-200,000 oncofetal antigen that is one of the more widely studied human tumor-associated antigens. This review will provide: (i) a brief overview of the CEA gene family, (ii) a summary of early preclinical findings on overcoming immune tolerance to CEA, and (iii) the rationale to develop mouse models which spontaneously develop gastrointestinal tumors and express the CEA transgene. Those models have been used extensively in the study of overcoming host immune tolerance to CEA, a self, tumor-associated antigen, and the experimental findings have served as the rationale for the design of early clinical trials to evaluate CEA-based cancer vaccines.
Topics: Animals; Cancer Vaccines; Carcinoembryonic Antigen; Disease Models, Animal; Humans; Mice; Mice, Transgenic; Neoplasms, Experimental; Survival Rate
PubMed: 15888344
DOI: 10.1016/j.mrfmmm.2004.10.014 -
Biosensors & Bioelectronics Jul 2019Simultaneous detection of multiple tumor biomarkers in body fluids could facilitate early diagnosis of lung cancer, so as to provide scientific reference for clinical...
Simultaneous detection of multiple tumor biomarkers in body fluids could facilitate early diagnosis of lung cancer, so as to provide scientific reference for clinical treatment. This paper depicted a multi-parameter paper-based electrochemical aptasensor for simultaneous detection of carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) in a clinical sample with high sensitivity and specificity. The paper-based device was fabricated through wax printing and screen-printing, which enabled functions of sample filtration and sample auto injection. Amino functional graphene (NG)-Thionin (THI)- gold nanoparticles (AuNPs) and Prussian blue (PB)- poly (3,4- ethylenedioxythiophene) (PEDOT)- AuNPs nanocomposites were synthesized respectively. They were used to modify the working electrodes not only for promoting the electron transfer rate, but also for immobilization of the CEA and NSE aptamers. A label-free electrochemical method was adopted, enabling a rapid simple point-of-care testing. Experimental results showed that the proposed multi-parameter aptasensor exhibited good linearity in ranges of 0.01-500 ng mL for CEA (R = 0.989) and 0.05-500 ng mL for NSE (R = 0.944), respectively. The limit of detection (LOD) was 2 pg mL for CEA and 10 pg mL for NSE. In addition, the device was evaluated using clinical serum samples and received a good correlation with large electrochemical luminescence (ECL) equipment, which would offer a new platform for early cancer diagnostics, especially in those resource-limit areas.
Topics: Biosensing Techniques; Carcinoembryonic Antigen; Electrochemical Techniques; Electrodes; Gold; Humans; Lung Neoplasms; Metal Nanoparticles; Microfluidics; Paper; Phosphopyruvate Hydratase
PubMed: 31039491
DOI: 10.1016/j.bios.2019.04.032 -
Cancer Genetics and Cytogenetics Nov 1983The tumor phenotype is associated with the rearrangement of genetic information and the altered expression of many gene products. In this review, genes associated with... (Review)
Review
The tumor phenotype is associated with the rearrangement of genetic information and the altered expression of many gene products. In this review, genes associated with the tumor phenotype have been arranged on the human gene map and indicate the extent to which the tumor phenotype involves the human genome. Nonrandom chromosomal aberrations that are frequently observed in tumors are presented. Altered metabolic demands of the tumor cell are reflected in altered gene expressions of a wide range of enzymes and other proteins, and these changed enzyme patterns are described. The study of oncogenes increasingly suggests that they may be significant in certain cancers, and the assignment of these genes has been tabulated. The biochemical and metabolic changes observed in tumors are complex; studying the patterns and interactions of these changes will aid our genetic understanding of the origins and development of tumors.
Topics: Carcinoembryonic Antigen; Cell Transformation, Neoplastic; Chromosome Aberrations; Chromosome Disorders; Chromosome Mapping; Enzymes; Genes; Hormones; Humans; Hybridomas; Membrane Proteins; Neoplasms; Oncogenes; Phenotype
PubMed: 6354430
DOI: 10.1016/0165-4608(83)90058-4 -
Medicine Jan 2022Malignant mesothelioma (MM) is difficult to diagnose because of the lack of parenchymal opacities, often revealing minimal or absent pleural thickening. Furthermore,...
Malignant mesothelioma (MM) is difficult to diagnose because of the lack of parenchymal opacities, often revealing minimal or absent pleural thickening. Furthermore, pleural effusion has diverse differential diagnoses, including malignancies, infections, as well as collagen vascular and other benign diseases. In general practice, lung cancer (LC) is the most common malignancy causing pleural effusion; therefore, a simple method using pleural diagnostic markers to differentiate between LC and mesothelioma is crucial.We retrospectively reviewed the data of 530 adult patients diagnosed with pleural effusion between January 2010 and December 2020 in an outpatient or inpatient setting. Patients with pathologically diagnosed MM or LC with cytologically positive (class IV or V) pleural effusion were analyzed, and the characteristics of these 2 diseases were compared.During the study period, 27 patients diagnosed with MM and 100 patients diagnosed with LC were enrolled. Receiver operating characteristic curve analysis demonstrated that pleural carcinoembryonic antigen (CEA) and hyaluronic acid (HA) could discriminate MM from LC with an area under the curve of 0.925 (95% confidence interval [CI]: 0.879-0.972, P < .001) and 0.815 (95% CI: 0.686-0.943, P < .001), respectively. To diagnose MM, the accuracy of pleural HA >30,000 ng/mL revealed a sensitivity of 75.0%, specificity of 72.6%, and odds ratio of 7.94 (95% CI: 2.5-25.2, P = .001); pleural CEA <6.0 ng/mL revealed a sensitivity of 95.2%, specificity of 84.9%, smaller negative likelihood ratio of 0.06, and odds ratio of 112.5% (95% CI: 14.4-878.1, P < .001). Multiple logistic regression analysis revealed that these 2 parameters could discriminate MM from LC, with a hazard ratio of 23.6 (95% CI: 2.437-228.1, P = .006) and 252.3 (95% Cl: 16.4-3888.1, P < .001), respectively, and their combination had a high specificity of 98.3%.Pleural CEA (≥6.0 ng/mL) can rule out MM with a high degree of certainty, and the positive results for combination of pleural CEA <6.0 ng/mL and HA >30,000 ng/mL can confirm MM with high specificity, prior to cytological or pathological examinations.
Topics: Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Humans; Hyaluronic Acid; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Pleural Effusion, Malignant; Retrospective Studies
PubMed: 35029914
DOI: 10.1097/MD.0000000000028517