scholarly journals TargetingO-Acetyl-GD2 Ganglioside for Cancer Immunotherapy

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Julien Fleurence ◽  
Sophie Fougeray ◽  
Meriem Bahri ◽  
Denis Cochonneau ◽  
Béatrice Clémenceau ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Immunotherapy ◽  
Target Selection ◽  
Tumor Biology ◽  
Target Antigen ◽  
T Cell Therapy ◽  
Normal Tissues ◽  
Therapy Development ◽  
Gd2 Ganglioside

Target selection is a key feature in cancer immunotherapy, a promising field in cancer research. In this respect, gangliosides, a broad family of structurally related glycolipids, were suggested as potential targets for cancer immunotherapy based on their higher abundance in tumors when compared with the matched normal tissues. GD2 is the first ganglioside proven to be an effective target antigen for cancer immunotherapy with the regulatory approval of dinutuximab, a chimeric anti-GD2 therapeutic antibody. Although the therapeutic efficacy of anti-GD2 monoclonal antibodies is well documented, neuropathic pain may limit its application.O-Acetyl-GD2, theO-acetylated-derivative of GD2, has recently received attention as novel antigen to target GD2-positive cancers. The present paper examines the role ofO-acetyl-GD2 in tumor biology as well as the available preclinical data of anti-O-acetyl-GD2 monoclonal antibodies. A discussion on the relevance ofO-acetyl-GD2 in chimeric antigen receptor T cell therapy development is also included.

scholarly journals Nonhuman primates express human leukemia-associated antigens

Blood ◽  
1984 ◽  
Vol 64 (5) ◽  
pp. 1074-1078
Author(s):  
JM Pesando ◽  
TA Conrad
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Nonhuman Primates ◽  
Lymphoblastic Leukemia ◽  
Adherent Cell ◽  
Human Leukemia ◽  
Papio Cynocephalus ◽  
Normal Tissues ◽  
Leukemia Antigen

Serologic studies using four murine monoclonal antibodies specific for the common acute lymphoblastic leukemia antigen (CALLA) and five monoclonal antibodies specific for the gp24 surface antigen indicate that these leukemia-associated antigens are present on cells of comparable tissues in man and in four nonhuman primates. As in man, adherent cell populations obtained from skin, lung, and bone marrow of Macaca fascicularis, M mulatta, M nemestrina, and Papio cynocephalus react with these antibodies. Similarly, granulocytes from both man and these nonhuman primates bind CALLA- and gp24-specific antibodies. Radioimmune precipitation experiments confirm the identity of these antigens. Our studies suggest that nonhuman primates can be used to screen serologic reagents to leukemia-associated antigens for potential toxic effects on normal tissues prior to their use in man. Similarly, nonhuman primates could be employed to assess the possible role of antigen-positive stromal cells in the reconstitution of bone marrow following transplantation.

scholarly journals Nonhuman primates express human leukemia-associated antigens

Blood ◽  
1984 ◽  
Vol 64 (5) ◽  
pp. 1074-1078 ◽  
Author(s):  
JM Pesando ◽  
TA Conrad
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Nonhuman Primates ◽  
Lymphoblastic Leukemia ◽  
Adherent Cell ◽  
Human Leukemia ◽  
Papio Cynocephalus ◽  
Normal Tissues ◽  
Leukemia Antigen

Abstract Serologic studies using four murine monoclonal antibodies specific for the common acute lymphoblastic leukemia antigen (CALLA) and five monoclonal antibodies specific for the gp24 surface antigen indicate that these leukemia-associated antigens are present on cells of comparable tissues in man and in four nonhuman primates. As in man, adherent cell populations obtained from skin, lung, and bone marrow of Macaca fascicularis, M mulatta, M nemestrina, and Papio cynocephalus react with these antibodies. Similarly, granulocytes from both man and these nonhuman primates bind CALLA- and gp24-specific antibodies. Radioimmune precipitation experiments confirm the identity of these antigens. Our studies suggest that nonhuman primates can be used to screen serologic reagents to leukemia-associated antigens for potential toxic effects on normal tissues prior to their use in man. Similarly, nonhuman primates could be employed to assess the possible role of antigen-positive stromal cells in the reconstitution of bone marrow following transplantation.

scholarly journals IMMU-15. PROTEOGENOMIC DISCOVERY OF NOVEL TUMOR PEPTIDES AS NEOANTIGENS FOR PERSONALIZED T CELL IMMUNOTHERAPY IN MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii362-iii363
Author(s):  
Samuel Rivero-Hinojosa ◽  
Melanie Grant ◽  
Aswini Panigrahi ◽  
Huizhen Zhang ◽  
Veronika Caisova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
High Risk ◽  
Tumor Cells ◽  
T Cell Response ◽  
Mass Spectrometry Data ◽  
Target Antigen ◽  
T Cell Therapy ◽  
Cd8 Cells ◽  
Normal Tissues

Abstract T cell immunotherapies are promising new tools to combat high-risk subgroups of medulloblastoma without increasing the late effects burden. The ideal target antigen of an effective antitumor T-cell response is abundantly expressed by tumor cells but not by normal tissues, in order to limit off-target effects. Tumors translate a host of highly novel transcripts that are the result of aberrations in tumor DNA and the unmasking of alternative or novel exons. We developed a novel proteogenomic approach to identify tumor-restricted peptides and used them to select and expand T cells capable of mounting a tumor-specific cytotoxic immune response. Using RNA-seq and WGS data, we created personalized custom searchable databases containing predicted novel proteins from somatic mutations, novel junctions and fusion transcripts from 56 medulloblastoma tumors. By searching these databases with raw mass spectrometry data from paired medulloblastoma tumors, we identified tens of neoantigen peptides arising from the translation of tumor-specific transcripts; novel isoforms being the predominant source. We tested these peptides for their ability to select and expand autologous polyclonal populations of T cells and tested the immunogenicity of each individual peptide. Flow cytometry revealed populations of CD4+ and CD8+ cells with an activation profile marked by IFN-γ and TNF-α. Immunosuppressive marker profiles were also characterized. Using cytotoxicity assays, we demonstrated that tumor specific T cells can eliminate neoantigen bearing tumor cells. Thus, proteogenomics can identify immunogenic tumor specific peptides that can be used to create a personalized, targeted T cell therapy for children with high risk medulloblastoma.

scholarly journals Systematic Pan-Cancer Analysis Reveals the Prognostic Value and Immunological Role of EPHX2

2021 ◽  
Author(s):  
Weiquan Hu ◽  
Qinfei Zhao ◽  
Jing Xu ◽  
Huaying Li ◽  
Longyu Zhu ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Prognostic Value ◽  
Immune Cell ◽  
Systematic Evaluation ◽  
Response Patterns ◽  
Clinical Value ◽  
Immune Modulators ◽  
Normal Tissues ◽  
Human Cancers

Abstract Background: Accumulating evidence indicates the essential role of EPHX2 in tumorigenesis. However, to date, no studies have performed a systematic evaluation of EPHX2 gene in human cancers and the predictive role of EPHX2 in cancer immunotherapy response has still not been explored. Methods: In the present study, Oncomine, TIMER2, UALCAN, GEPIA2, PrognoScan, HPA and Kaplan-Meier Plotter database were utilized to comprehensively analyze the expression landscape and prognostic clinical value of EPHX2 across 33 human cancers. To gain a better understanding of the role of EPHX2 in cancer immunotherapy, the correlations between EPHX2 and tumor immune microenvironment (TME) such as immune cell infiltrations, immune modulators, and the major histocompatibility complex were demonstrated. The underlying EPHX2-associated signaling pathways in cancer were also analysed. Moreover, the correlation between EPHX2 and immunotherapeutic biomarkers such as tumor mutational burden (TMB) and microsatellite instability (MSI) was explored. At last, the potential immune checkpoint blockers (ICB) response was predicted using tumor immune dysfunction and exclusion (TIDE) algorithm. Results: Overall, the mRNA expression of EPHX2 was significantly downregulated in the majority of tumors compared with normal tissues. Despite the significant prognostic value of EPHX2 expression across cancers, EPHX2 played a protective or detrimental role in different kinds of cancers. Generally speaking, immune cell infiltrations, immune modulators and immunotherapeutic biomarkers were all strongly related to the expression of EPHX2. Besides, EPHX2 expression was significantly related to immune-relevant pathways, especially in PAAD, THYM and UVM. Furthermore, our study demonstrated diverse response patterns of ICB in response to EPHX2 expression in different tumor types. Conclusion: Our findings here suggest that EPHX2 could be a prognostic factor in multiple cancers and play an important role in tumor immunity by affecting infiltrating immune cells, TMB and MSI. This study provides further insight into the role of EPHX2 in tumor immunotherapy.

scholarly journals Systematic Pan-Cancer Analysis Reveals the Prognostic Value and Immunological Role of EPHX2

2022 ◽  
Author(s):  
Weiquan Hu ◽  
Qinfei Zhao ◽  
Jing Xu ◽  
Huaying Li ◽  
Longyu Zhu ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Prognostic Value ◽  
Immune Cell ◽  
Systematic Evaluation ◽  
Response Patterns ◽  
Clinical Value ◽  
Immune Modulators ◽  
Normal Tissues ◽  
Human Cancers

Abstract Background Accumulating evidence indicates the essential role of EPHX2 in tumorigenesis. However, to date, no studies have performed a systematic evaluation of EPHX2 gene in human cancers and the predictive role of EPHX2 in cancer immunotherapy response has still not been explored. Methods In the present study, Oncomine, TIMER2, UALCAN, GEPIA2, PrognoScan, HPA and Kaplan-Meier Plotter database were utilized to comprehensively analyze the expression landscape and prognostic clinical value of EPHX2 across 33 human cancers. To gain a better understanding of the role of EPHX2 in cancer immunotherapy, the correlations between EPHX2 and tumor immune microenvironment (TME) such as immune cell infiltrations, immune modulators, and the major histocompatibility complex were demonstrated. The underlying EPHX2-associated signaling pathways in cancer were also analysed. Moreover, the correlation between EPHX2 and immunotherapeutic biomarkers such as tumor mutational burden (TMB) and microsatellite instability (MSI) was explored. At last, the potential immune checkpoint blockers (ICB) response was predicted using tumor immune dysfunction and exclusion (TIDE) algorithm. Results Overall, the mRNA expression of EPHX2 was significantly downregulated in the majority of tumors compared with normal tissues. Despite the significant prognostic value of EPHX2 expression across cancers, EPHX2 played a protective or detrimental role in different kinds of cancers. Generally speaking, immune cell infiltrations, immune modulators and immunotherapeutic biomarkers were all strongly related to the expression of EPHX2. Besides, EPHX2 expression was significantly related to immune-relevant pathways, especially in PAAD, THYM and UVM. Furthermore, our study demonstrated diverse response patterns of ICB in response to EPHX2 expression in different tumor types. Conclusion Our findings here suggest that EPHX2 could be a prognostic factor in multiple cancers and play an important role in tumor immunity by affecting infiltrating immune cells, TMB and MSI. This study provides further insight into the role of EPHX2 in tumor immunotherapy.

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

Role of TWEAK and Fn14 in tumor biology

10.2741/2270 ◽  
2007 ◽  
Vol 12 (1) ◽  
pp. 2761 ◽  
Author(s):  
Jeffrey, A. Winkles
Keyword(s):  
Tumor Biology

NOB1: A Potential Biomarker or Target in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 1081-1089
Author(s):  
Weiwei Ke ◽  
Zaiming Lu ◽  
Xiangxuan Zhao
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Binding Protein ◽  
Tumor Development ◽  
Anticancer Therapy ◽  
Research Progress ◽  
Normal Tissues ◽  
Potential Biomarker

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

scholarly journals The Role of Monoclonal Antibodies in Smoldering and Newly Diagnosed Transplant-Eligible Multiple Myeloma

2020 ◽  
Vol 13 (12) ◽  
pp. 451
Author(s):  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Paola Deias ◽  
Francesca Patriarca
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Survival Outcomes ◽  
Newly Diagnosed ◽  
Cellular Targets ◽  
Recent Introduction

The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a significant price in terms of toxicity. In smoldering MM, MoAbs have been applied, either alone or in combination with other drugs, with the goal of delaying the progression to active MM and restoring the immune system. In this review, we will focus on the main results achieved so far and on the main on-going trials using MoAbs in SMM and NDTEMM.

Sign in / Sign up

Export Citation Format

Share Document