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World Journal of Gastrointestinal Oncology 2015年第12期7卷 492-502页

作者： Anil Suri Nirmala Jagadish Shikha Saini Namita Gupta Cancer Microarray Genes and Proteins Laboratory National Institute of Immunology

Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.

关键词： Cancer testis antigens Colorectal cancer Testis sp

Reaction of antibodies to Campylobacter jejuni and cytolethal distending toxin B with tissues and food antigens

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World Journal of Gastroenterology 2019年第9期25卷 1050-1066页

作者： Aristo Vojdani Elroy Vojdani Immunosciences Lab. Inc. Los Angeles Cyrex Labs LLC. Phoenix Department of Preventive Medicine Loma Linda University School of Medicine Regenera Medical Los Angeles

BACKGROUND The bacteria Campylobacter jejuni(C. jejuni) is commonly associated with GuillaneBarré syndrome(GBS) and irritable bowel syndrome(IBS), but studies have also linked it with Miller Fisher syndrome, reactive arthritis and other disorders, some of which are autoimmune. It is possible that C. jejuni and its toxins may be crossreactive with some human tissues and food antigens, potentially leading to autoimmune *** To measure the immune reactivity of C. jejuni and C. jejuni cytolethal distending toxin(Cdt) antibodies with tissue and food antigens to examine their role in *** Using enzyme-linked immunosorbent assay(ELISA) methodology, specific antibodies made against C. jejuni and C. jejuni Cdt were applied to a variety of microwell plates coated with 45 tissues and 180 food antigens. The resulting immunoreactivities were compared to reactions with control wells coated with human serum albumin(HSA) which were used as negative controls and with wells coated with C. jejuni lysate or C. jejuni Cdt which served as positive *** At 3 SD above the mean of control wells coated with HSA or 0.41 OD, the mouse monoclonal antibody made against C. jejuni showed moderate to high reactions with zonulin, somatotropin, acetylcholine receptor, β-amyloid and *** immune reaction was low with an additional 25 tissue antigens including asialoganglioside, and the same antibody did not react at all with another 15 tissue antigens. Examining the reaction between C. jejuni antibody and 180 food antigens, we found insignificant reactions with 163 foods but low to high immune reactions with 17 food antigens. Similarly, we examined the reaction of C. jejuni Cdt with the same tissues and food antigens. The strongest reactions were observed with zonulin, intrinsic factor and somatotropin. The reaction was moderate with 9 different tissue antigens including thyroid peroxidase, and reaction was low with another 10 different antigens, includ

关键词： Campylobacter jejuni Cytolethal distending toxin Tissue antigens Food antigens Autoimmune reactivities Cross-reactivity

Identification of tumor antigens and immune subtypes of hepatocellular carcinoma for mRNA vaccine development

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World Journal of Gastrointestinal Oncology 2023年第10期15卷 1717-1738页

作者： Tai-Liang Lu Cheng-Long Li Yong-Qiang Gong Fu-Tao Hou Chao-Wu Chen Department of General Surgery Hunan Provincial People’s HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 410005Hunan ProvinceChina

BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and suitable subpopu-lations for mRNA *** Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome *** with somatic mutations and copy number variations were identified by cBioPortal *** differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website *** Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells(APCs).Tumor-associated antigens were overexpressed in tumors and associated with prognosis,genomic alterations,and APC infiltration.A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune *** weighted gene coexpression network analysis(WGCNA)was used to determine the candidate biomarker molecules for appropriate populations for mRNA *** subtypes showed distinct cellular and clinical *** IS1 and IS3 immune subtypes were immunologically“cold”.The IS2 and IS4 immune subtypes were immunologically“hot”,and the immune checkpoint genes and immunogenic cell death genes were upregulated in these ***1-related modules were identified with the WGCNA ***,five hub genes(RBP4,KNG1,METTL7A,F12,and ABAT)were identified,and they might be potential biomarkers for mRNA *** AURKA,CCNB1,CDC25C,CDK1,TRIP13,PES1,MCM3,PPM1G,NEK2,KIF2C,PTTG1,KPNA2,and PRC1 have been identified as candidate HCC antigens for mRNA vaccine *** IS1 and IS3 immune subtypes are suitable populations for mRNA ***4,KNG1,METTL7A,F12,and ABAT are potential biomark

关键词： mRNA vaccine Hepatocellular carcinoma Immunotype antigens Immune subtypes

Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens

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World Journal of Gastroenterology 2018年第48期24卷 5418-5432页

作者： Sandra Wagner Christina S Mullins Michael Linnebacher Section of Molecular Oncology and Immunotherapy General SurgeryUniversity Medical Center

Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.

关键词： Cancer vaccines Colorectal neoplasm Immunotherapy Neoplasm antigen tumor-associated antigens tumor-specific antigens Neoantigen(s)

STUDIES ON SPECIFIC SEROLOGICAL antigens IN METACERCARIAE AND JUVENILES OF Paragoniums westermani AND ITS MONOCLONAL ANTIBODIES

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Science China Chemistry 1990年第2期33卷 178-187页

作者：蒋作君沈一平赵慰先 Nanjing Medical College Nanking 210005 PRC

The polyclonal antibodies to juveniles of Paragoniums westermani (PwJ-PcAbs) from sera of Wistar rats infected with Paragoniums westerrnani (P. w.)were purified by Sephadex G 200 chromatography. Next the shared serological antigens of P. w. metacercaria and juveniles (PwMJ-SAg) from the crude antigens of the metacercariae (M-NS-Ag) were purified with immuno-affinity chromatography on cyanogen bromide-activated cross-linked Sepharose 4B beads coupled withPwJ-PcAbs. PwMJ-SAg, agroup of glycoprotein molecules shown by the staining test, were specific serological antigens of P. w. metacercariae and juveniles, identified by the immunoabsorb test and immunoelectrophoresis. By SDSPAGE, PwMJ-SAg were fractionated to seven bands, including major bands A(***) and Bi(19.5 K), the two major serological antigen molecules. 20 sera samples from the patients with the nonpulmonary type of P. w. paragonimiasis were detected using PwMJ-SAg and M-NS-Ag by Dot-ELISA, and the difference of sensitivity between two antigens was highly statistically significant (P<0.001). BALB/c mice, in the early stage of infection with P. w. metacercaria, were immunized with PwMJ-SAg. The spleen cells of the mice were isolated and fused with SP_2/o, a murine myeloma cell line. After three subclonal cultures, eight cell lines secreting monoclonal antibodies (McAbs) to PwMJ-SAg were prepared from 384 wells of hybridoma cells. All McAbs were IgG_1 subclass.

关键词： paragonimiasis serological antigens monoclonal antibodies diagnosis.

Detection of urinary antigens and their seroreactivity with serum of patients in Leishmania donovani infection

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Asian Pacific Journal of Tropical Medicine 2011年第5期4卷 367-370页

作者： Vinod Kumar Jalaj Kumar Gour Surabhi Bajpai Manish Mishra Rakesh Kumar Singh Molecular Immunology Laboratory Department of BiochemistryFaculty of ScienceBanaras Hindu UniversityVaranasi-221005India

Objective:To detect leishmanial antigens in pre and post treated urine of visceral leishmaniasis (VL) ***:Urine and serum sample from three VL patients were collected. Ammonium sulphate precipitation and purification of urine sample was done for proteins *** PAGE of proteins was done followed by western blotting,with the patient’s pre and post treatment ***:Eight proteins of molecular weights 17 kDa,25 kDa,28 kDa,42 kDa, 47 kDa,54 kDa,60 kDa and 85 kDa were detected in the urine of VL patients before treatment. After treatment with miltefosine,none of the above proteins was detected in urine *** western blot analysis with pre treatment serum confirmed the antigenicity of four urinary proteins of molecular weights 25 kDa,28 kDa,54 kDa and 60 *** seropositivity with 25 kDa and 28 kDa antigens was negative with serum obtained after the completion of ***:In the context to unavailability of a prognostic tool,urinary leishmanial antigens may offer a better choice and may also be useful as immunoprophylactic candidates.

关键词： Visceral leishmaniasis Urinary antigens Seroreactivity

Hepatitis C virus antigens enzyme immunoassay for one-step diagnosis of hepatitis C virus coinfection in human immunodeficiency virus infected individuals

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World Journal of Hepatology 2019年第5期11卷 442-449页

作者： Ke-Qin Hu Wei Cui Susan D Rouster Kenneth E Sherman Division of GI/Hepatology University of CaliforniaIrvineSchool of MedicineOrangeCA 92868United States Division of Digestive Diseases University of Cincinnati College of MedicineCincinnatiOH 45267United States

BACKGROUND Current diagnosis of hepatitis C virus(HCV)infection requires two sequential steps:testing for anti-HCV followed by HCV RNA PCR to confirm *** have developed a highly sensitive and specific HCV-antigens enzyme immunoassay(HCV-Ags EIA)for one-step diagnosis of viremic HCV *** To assess the clinical application of the HCV-Ags EIA in one-step diagnosis of viremic HCV infection in human immunodeficiency virus(HIV)-coinfected *** The study blindly tested HCV-Ags EIA for its performance in one-step diagnosing viremic HCV infection in 147 sera:10 without HCV or HIV infection;54 with viremic HCV monoinfection;38 with viremic HCV/HIV coinfection;and 45 with viremic HCV and non-viremic HIV *** Upon decoding,it was 100%accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR *** five sera with HCV infection,HCV RNA was as low as 50-59 IU/mL,and four out of five tested positive for HCV-Ags ***,it was also 100%accordance of HCV-Ags EIA to HCV infection status by HCV RNA PCR in 83 sera with HCV and HIV coinfection,regardless if HIV infection was active or *** The modified HCV-Ags EIA has a lower detection limit equivalent to serum HCV RNA levels of approximately 100 IU/*** is highly sensitive and specific in the setting of HIV coinfection,regardless of HIV infection status and CD4 *** data support the clinical application of the HCV-Ags EIA in one-step diagnosis of HCV infection in HIV-infected individuals.

关键词： Hepatitis C virus Hepatitis C virus antigens Hepatitis C virus core antigen Hepatitis C virus diagnostic test Diagnostic assay Enzyme immunoassay

Comparison of antibody detection with <i>Blastomycesdermatitidis</i>yeast lysate antigens in serum specimens from immunized rabbits and infected dogs

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Open Journal of Immunology 2011年第3期1卷 74-79页

作者： Will Christenson Rachel Horton Kayla Campbell Kelly Meacham Amber Schroeder Gene M. Scalarone Department of Biological Sciences Idaho State University

This present study was designed to evaluate B. dermatitidis antigens, prepared from two isolates (B5896, 597), when the yeast cells were allowed to lyse in distilled water for one day or seven days. The indirect enzyme-linked immunosorbent assay (ELISA) was used to determine the ability of the lysate reagents to detect antibodies in 30 rabbit and 30 dog serum specimens. Mean absorbance values with B5896 lysate antigen ranged from 1.637 (day 1) to 1.461 (day 7) and absorbance values with 597 antigen ranged from 1.579(day 1) to 1.396 (day 7) with the serum specimens from immunized rabbits. Serum specimens from infected dogs yielded absorbance values ranging from 1.672 (day 1) to 1.763 (day 7) with the B5896 and values ranging from 1.909 (day 1) to 1.224 (day 7) with the 597. Optimal reactivity was obtained with the day 1 lysate using both lysate antigens against the rabbit sera and with the 597 antigen against the dog sera. Slightly greater reactivity was evidenced with the day 7 B5896 antigen when the dog sera was tested. Comparative studies are continuing in order to produce an optimal anti-genic preparation for antibody detection in blastomycosis.

关键词： ELISA Blastomycesdermatitidis Antibody Detection Lysate antigens

Cross-Reaction between Gliadin and Different Food and Tissue antigens

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Food and Nutrition Sciences 2013年第1期4卷 20-32页

作者： Aristo Vojdani Igal Tarash Immunosciences Lab. Inc. Los Angeles USA Immunosciences Lab. Inc. Los Angeles USA&Cyrex Labs LLC. Phoenix USA.

A subgroup of coeliac disease patients continues to experience symptoms even on a gluten-free diet (GFD). We attempted to determine whether these symptoms could be due to either cross-contamination with gluten-containing foods or cross-reactivity between α-gliadin and non-gluten foods consumed on a GFD. We measured the reactivity of affinity-purified polyclonal and monoclonal α-gliadin 33-mer peptide antibodies against gliadin and additional food antigens commonly consumed by patients on a GFD using ELISA and dot-blot. We also examined the immune reactivity of these antibodies with various tissue antigens. We observed significant immune reactivity when these antibodies were applied to cow’s milk, milk chocolate, milk butyrophilin, whey protein, casein, yeast, oats, corn, millet, instant coffee and rice. To investigate whether there was cross-reactivity between α-gliadin antibody and different tissue antigens, we measured the degree to which this antibody bound to these antigens. The most significant binding occurred with asialoganglioside, hepatocyte, glutamic acid decarboxylase 65, adrenal 21-hydroxylase, and various neural antigens. The specificity of anti-α-gliadin binding to different food and tissue antigens was demonstrated by absorption and inhibition studies. We also observed significant cross-reactivity between α-gliadin 33-mer and various food antigens, but some of these reactions were associated with the contamination of non-gluten foods with traces of gluten. The consumption of cross-reactive foods as well as gluten-contaminated foods may be responsible for the continuing symptoms presented by a subgroup of patients with coeliac disease. The lack of response of some CD patients may also be due to antibody cross-reactivity with non-gliadin foods. These should then be treated as gluten-like peptides and should also be excluded from the diet when the GFD seems to fail.

关键词： Cross-Reaction Gliadin Food antigens Tissue antigens Celiac Disease Gluten-Free Diet

Expression of hepatitis B virus surface antigens induces defective gonad phenotypes in Caenorhabditis elegans

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World Journal of Virology 2017年第1期6卷 17-25页

作者： Yi-Yin Chen Li-Wei Lee Wei-Ning Hong Szecheng J Lo Department of Biomedical Science College of Medicine Chang Gung University Graduate Institute of Biomedical Science College of Medicine Chang Gung University

AIM To test whether a simple animal, Caenorhabditis elegans(C. elegans), can be used as an alternative model to study the interaction between hepatitis B virus antigens(HBs Ag) and host factors. METHODS Three plasmids that were able to express the large, middle and small forms of HBs Ags(LHBs Ag, MHBs Ag, and SHBs Ag, respectively) driven by a ubiquitous promoter(fib-1) and three that were able to express SHBs Ag driven by different tissue-specific promoters were constructed and microinjected into worms. The brood size, egglaying rate, and gonad development of transgenic worms were analyzed using microscopy. Levels of m RNA related to endoplasmic reticulum stress, enpl-1, hsp-4, pdi-3 and xbp-1, were determined using reverse transcription polymerase reaction(RT-PCRs) in three lines of transgenic worms and dithiothreitol(DTT)-treated wild-type worms. RESULTS Severe defects in egg-laying, decreases in brood size, and gonad retardation were observed in transgenic worms expressing SHBs Ag whereas moderate defects were observed in transgenic worms expressing LHBs Ag and MHBs Ag. RT-PCR analysis revealed that enpl-1, hsp-4 and pdi-3 transcripts were significantly elevated in worms expressing LHBs Ag and MHBs Ag and in wild-type worms pretreated with DTT. By contrast, only pdi-3 was increased in worms expressing SHBs Ag. To further determine which tissue expressing SHBs Ag could induce gonad retardation, we substituted the fib-1 promoter with three tissue-specific promoters(myo-2 for the pharynx, est-1 for the intestines and mec-7 for the neurons) and generated corresponding transgenic animals. Moderate defective phenotypes were observed in worms expressing SHBs Ag in the pharynx and intestines but not in worms expressing SHBs Ag in the neurons, suggesting that the secreted SHBs Ag may trigger a cross-talk signal between the digestive track and the gonad resulting in defective phenotypes. CONCLUSION Ectopic expression of three forms of HBs Ag that causes recognizable pheno

关键词： Hepatitis B virus Caenorhabditis elegans Green fluorescence proteins Endoplasmic reticulum stress Gonad retardation Surface antigens