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Wim J. G. Oyen - One of the best experts on this subject based on the ideXlab platform.
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tumor to cervical spinal cord standardized uptake ratio sur improves the reproducibility of f 18 fdg pet based tumor segmentation in head and neck squamous cell carcinoma in a multicenter setting
Radiotherapy and Oncology, 2019Co-Authors: Sven Van Den Bosch, Tim Dijkema, Marielle E.p. Philippens, Chris H J Terhaard, Frank Hoebers, Johannes H A M Kaanders, Wim J. G. OyenAbstract:Abstract Background In quantitative FDG-PET data analysis, normalization of the standardized uptake value (SUV) with an Internal Image-derived standard improves its reproducibility. In this study, the cervical spinal cord is proposed as an Internal standard that is within the field of view of the radiotherapy planning PET/CT-scan in head and neck cancer. The aim is to evaluate if the tumor to cervical spinal cord standardized uptake ratio (SUR) can improve the reproducibility of a model to determine the metabolic tumor volume (MTV) on FDG-PET/CT in a multicenter setting. Materials and methods Ninety-five radiotherapy planning FDG-PET/CT-scans of patients with head and neck cancer were analyzed using the Bland–Altman method to evaluate differences in FDG-uptake in the cervical spinal cord and the mediastinal blood pool. Non-linear regression analysis was used to determine the optimal MTV using the gross tumor volume (GTV) as ground truth and a spatial overlap-index as statistical validation metric. Reproducibility was evaluated using the Bland-Altman method and external validation was performed in an independent dataset consisting of 62 patients. Results Bland–Altman’s analyses demonstrated equivalence of FDG-uptake in the mediastinal blood pool and the cervical spinal cord. Reproducibility of the models improved when using SUR instead of SUV. These results were confirmed in the validation cohort. Conclusion The use of the tumor to cervical spinal cord SUR instead of SUV improves the reproducibility of a model to determine the MTV on FDG-PET/CT in a multicenter setting. This study indicates that SUR may be preferred over SUV based approaches.
Alain Friboulet - One of the best experts on this subject based on the ideXlab platform.
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novel peptide inhibiting both tem 1 β lactamase and penicillin binding proteins
FEBS Journal, 2010Co-Authors: Denis Phichith, Jean-marie Frère, Moreno Galleni, Severine Padiolleaulefevre, Adeline Guellier, Soun Banh, Alain Friboulet, Daniel Thomas, Berangere AvalleAbstract:9G4H9, a catalytic antibody displaying β-lactamase-like activity, has been developed by the anti-idiotypic approach using β-lactamase as the first antigen. Thus 9G4H9 represents the ‘Internal Image‘ of β-lactamase. We selected a cyclic peptide anchored to a bacteriophage M13 library using 9G4H9 as the target. Pep90 is a cyclic heptapeptide enclosed between two cysteine residues. We showed that Pep90 could inhibit both TEM-1 β-lactamase (Ki = 333 μm) and several penicillin-binding proteins (IC50 values ranging from 6–62 μm). We determined that the tryptophan residue of Pep90 is of crucial importance for its inhibitory activity. Using Pep90 as a scaffold, we generated a new class of peptidomimetics that retained inhibitory activity towards TEM-1 β-lactamase.
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Idiotypic network mimicry and antibody catalysis: lessons for the elicitation of efficient anti-idiotypic protease antibodies.
Journal of Immunological Methods, 2002Co-Authors: D. Pillet, M. Paon, I.i. Vorobiev, A.g. Gabibov, D. Thomas, Alain FribouletAbstract:An important challenge in the field of catalytic antibodies is the generation of antibodies with designed sequence-specific protease activities. Such catalysts would not only be recruited for diverse applications in basic biological science, but could also offer new approaches in biotechnology and medicine. We have previously used the "Internal Image" property of the idiotypic network to elicit antibodies with efficient esterase and amidase activities. In the present report, we present preliminary results for the production of anti-idiotypic antibodies mimicking subtilisin. A monoclonal inhibitory antibody of subtilisin was characterized and used to elicit anti-idiotypic antibodies. Some of these antibodies exhibit not only an amidase activity against synthetic substrates, but are also able to cleave a protein, bovine serum albumin (BSA).
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functional mimicry elicitation of a monoclonal anti idiotypic antibody hydrolizing beta lactams
The FASEB Journal, 1998Co-Authors: Berangere Avalle, Daniel Thomas, Alain FribouletAbstract:Antigen mimicry by anti-idiotypic antibodies is investigated as a reliable strategy to achieve molecular imprinting of an enzymatic activity. A monoclonal anti-idiotypic antibody (Ab2-9G4H9) was elicited by using a monoclonal antibody (Ab1-7AF9) specific for the beta-lactamase active site. Catalytic features of Ab2 were characterized with beta-lactamase substrates. The antibody combining site appeared to have retained a part of the catalytic specificity. The relevance of the idiotypic mimicry concept for the generation of catalytic antibodies was further demonstrated by eliciting a third generation antibody (Ab3), which was shown to recognize beta-lactamase: the complete Internal Image properties of Ab2 9G4H9, including binding and catalytic properties, were thus checked.
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Abzyme generation using an anti-idiotypic antibody as the "Internal Image" of an enzyme active site.
Applied biochemistry and biotechnology, 1994Co-Authors: Alain Friboulet, L Izadyar, Berangere Avalle, A RosetoAbstract:Since the two reports published in 1986 by the laboratories of R. Lerner and P. G. Schultz, it has been clearly established that antibodies may be induced to act as catalysts in numerous chemical reactions. In all cases, catalytic antibodies were elicited using a substrate-based approach. In the present article, we propose an alternative and complementary enzyme-based approach to generate catalytic antibodies. This approach uses the properties of anti-idiotypic antibodies to generate Internal Images of enzyme active sites. Experimental results are discussed for polyclonal and monoclonal anti-idiotypic antibodies.
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Monoclonal anti-idiotypic antibodies as functional Internal Images of enzyme active sites. Production of a catalytic antibody with a cholinesterase activity
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: L Izadyar, A Roseto, Alain Friboulet, Marie Helene Remy, Daniel ThomasAbstract:Abstract Monoclonal antibody 9A8 was selected by immunizing mice with AE-2, a monoclonal antibody directed against the active site of acetylcholinesterase. In accordance with the idiotypic network theory, monoclonal anti-idiotypic antibody 9A8 displayed Internal-Image properties of the original immunogen, the acetylcholinesterase active site. Hydrolysis of acetylthiocholine and related esters of thiocholine by 9A8 follows saturation kinetics and kinetic parameters were determined. The hydrolytic activity is characterized by a lowered kcat value (81 s-1) and an increased Km value (0.6 mM) when compared with the original enzyme. However, the rate acceleration (kcat/kuncat = 4.15 x 10(8) remains higher than for the esterase activities usually described for catalytic antibodies directed against transition-state analogs. The 9A8 activity exhibits a relaxation of specificity toward both substrates and inhibitors. This specificity does not correspond to a known enzymatic activity. The anti-idiotypic approach should be valuable for producing different structural and functional copies of the same enzyme active site. This should allow further insights into structure-activity relationships. Furthermore, use of chemically modified enzymes as immunogens may result in anti-idiotypic antibodies with catalytic activities not found in the native enzymes.
Daniel Thomas - One of the best experts on this subject based on the ideXlab platform.
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novel peptide inhibiting both tem 1 β lactamase and penicillin binding proteins
FEBS Journal, 2010Co-Authors: Denis Phichith, Jean-marie Frère, Moreno Galleni, Severine Padiolleaulefevre, Adeline Guellier, Soun Banh, Alain Friboulet, Daniel Thomas, Berangere AvalleAbstract:9G4H9, a catalytic antibody displaying β-lactamase-like activity, has been developed by the anti-idiotypic approach using β-lactamase as the first antigen. Thus 9G4H9 represents the ‘Internal Image‘ of β-lactamase. We selected a cyclic peptide anchored to a bacteriophage M13 library using 9G4H9 as the target. Pep90 is a cyclic heptapeptide enclosed between two cysteine residues. We showed that Pep90 could inhibit both TEM-1 β-lactamase (Ki = 333 μm) and several penicillin-binding proteins (IC50 values ranging from 6–62 μm). We determined that the tryptophan residue of Pep90 is of crucial importance for its inhibitory activity. Using Pep90 as a scaffold, we generated a new class of peptidomimetics that retained inhibitory activity towards TEM-1 β-lactamase.
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Enzyme mimicry by the antiidiotypic antibody approach
Proceedings of the National Academy of Sciences of the United States of America, 2000Co-Authors: Alexander V. Kolesnikov, Berangere Avalle, A. V. Kozyr, Elena Sergeevna Alexandrova, Frederic Koralewski, Alexander V. Demin, Mikhail I. Titov, Alfonso Tramontano, Sudhir Paul, Daniel ThomasAbstract:The concept of "Internal Image" of antiidiotypic antibodies has provided the basis for eliciting catalytic antibodies. A monoclonal IgM 9A8 that was obtained as an antiidiotype to AE-2 mAb, a known inhibitor of acetylcholinesterase, displayed esterolytic activity. Study of recombinant Fab fragments and separate light and heavy chains of 9A8 confirmed that the antibody variable domain encodes the catalytic function, whereas neither part of the primary sequence of the Fab exhibited homology with the enzyme. The specific modification of the 9A8 variable domain by an active site-directed covalent inhibitor revealed the presence of an active site Ser residue. A three-dimensional modeling suggests the existence of a functional catalytic dyad Ser-His. Comparison of active sites of 9A8 and 17E8 esterolytic abzyme raised against transition-state analog revealed structural similarity although both antibodies were elicited by two different approaches.
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functional mimicry elicitation of a monoclonal anti idiotypic antibody hydrolizing beta lactams
The FASEB Journal, 1998Co-Authors: Berangere Avalle, Daniel Thomas, Alain FribouletAbstract:Antigen mimicry by anti-idiotypic antibodies is investigated as a reliable strategy to achieve molecular imprinting of an enzymatic activity. A monoclonal anti-idiotypic antibody (Ab2-9G4H9) was elicited by using a monoclonal antibody (Ab1-7AF9) specific for the beta-lactamase active site. Catalytic features of Ab2 were characterized with beta-lactamase substrates. The antibody combining site appeared to have retained a part of the catalytic specificity. The relevance of the idiotypic mimicry concept for the generation of catalytic antibodies was further demonstrated by eliciting a third generation antibody (Ab3), which was shown to recognize beta-lactamase: the complete Internal Image properties of Ab2 9G4H9, including binding and catalytic properties, were thus checked.
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Monoclonal anti-idiotypic antibodies as functional Internal Images of enzyme active sites. Production of a catalytic antibody with a cholinesterase activity
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: L Izadyar, A Roseto, Alain Friboulet, Marie Helene Remy, Daniel ThomasAbstract:Abstract Monoclonal antibody 9A8 was selected by immunizing mice with AE-2, a monoclonal antibody directed against the active site of acetylcholinesterase. In accordance with the idiotypic network theory, monoclonal anti-idiotypic antibody 9A8 displayed Internal-Image properties of the original immunogen, the acetylcholinesterase active site. Hydrolysis of acetylthiocholine and related esters of thiocholine by 9A8 follows saturation kinetics and kinetic parameters were determined. The hydrolytic activity is characterized by a lowered kcat value (81 s-1) and an increased Km value (0.6 mM) when compared with the original enzyme. However, the rate acceleration (kcat/kuncat = 4.15 x 10(8) remains higher than for the esterase activities usually described for catalytic antibodies directed against transition-state analogs. The 9A8 activity exhibits a relaxation of specificity toward both substrates and inhibitors. This specificity does not correspond to a known enzymatic activity. The anti-idiotypic approach should be valuable for producing different structural and functional copies of the same enzyme active site. This should allow further insights into structure-activity relationships. Furthermore, use of chemically modified enzymes as immunogens may result in anti-idiotypic antibodies with catalytic activities not found in the native enzymes.
Soldano Ferrone - One of the best experts on this subject based on the ideXlab platform.
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functional idiotopes tumor antigen directed expression of cd8 t cell epitopes nested in unique nh2 terminal vh sequence of antiidiotypic antibodies
Cancer Research, 2005Co-Authors: Kouichiro Kawano, Soldano Ferrone, Constantin G IoannidesAbstract:Antiidiotypic antibodies have been and are being used for cancer immunotherapy based on the rationale that Ab2 carrying an “Internal Image” of the corresponding tumor antigen can induce tumor antigen–specific antibodies (i.e., Ab3 and inhibit tumor growth). Recent evidence indicates that Ab2 also induces cellular responses by CD4+ and CD8+ T cells. This finding has raised the question of where the short peptides, which express CD8+ T-cell–defined epitopes, are located and their relationship with the tumor antigen. We found that two of the four known Ab2 associated with tumor antigen, with known amino acid sequence, express unique NH2-terminal VH sequences which precede the framework regions. Both the unique and the shared NH2-terminal VH sequences are nested MHC class I antigen–binding peptides. These peptides were highly homologous with peptides from corresponding tumor antigen (carcinoembryonic antigen, CD55, and human high molecular weight melanoma–associated antigen) but differed from the tumor antigen peptides by the presence of the side chain known to mediate stronger forces of interaction with other atoms. The presence of candidate CTL epitopes in NH2-terminal VH of Ab2 homologous with tumor antigen may be important for the development of novel immunotherapeutic strategies for cancer.
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antiantiidiotypic response and clinical course of the disease in patients with malignant melanoma immunized with mouse antiidiotypic monoclonal antibody mk2 23
Hybridoma, 1995Co-Authors: Abraham Mittelman, Xinhui Wang, Kazuhiko Matsumoto, Soldano FerroneAbstract:An active specific immunotherapy trial has been implemented in patients with malignant melanoma utilizing the mouse anti-id MAb MK2-23. The latter bears the Internal Image of the determinant by the anti-HMW-MAA MAb 763.74. The immunogenicity of anti-id MAb MK2-23 is enhanced by conjugation to a carrier and administration with an adjuvant. Anti-id MAb MK2-23 induced humoral anti-HMW-MAA immunity in about 60% of the immunized patients. The latter was associated with a statistically significant survival prolongation. It is suggested that anti-HMW-MAA immunity may have a beneficial effect on the clinical course of the disease by inhibiting the function of HMW-MAA in the biology of melanoma cells.
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kinetics of the immune response and regression of metastatic lesions following development of humoral anti high molecular weight melanoma associated antigen immunity in three patients with advanced malignant melanoma immunized with mouse antiidiotypi
Cancer Research, 1994Co-Authors: Abraham Mittelman, Zhi Jian Chen, C C Liu, S Hirai, Soldano FerroneAbstract:Active specific immunotherapy has been implemented in patients with advanced malignant melanoma, utilizing the mouse antiidiotypic (anti-id) monoclonal antibody (mAb) MK2-23 which bears the Internal Image of high molecular weight-melanoma associated antigen (HMW-MAA). In a previous study, development of anti-HMW-MAA immunity in patients with advanced malignant melanoma immunized with anti-id mAb MK2-23 was found to be associated with a statistically significant survival prolongation. Since no Information is available about the relationship between development of immunity and clinical response in patients immunized with anti-id mAb, the present study has characterized the kinetics of the immune response in three patients with advanced malignant melanoma who experienced regression of metastatic lesions following immunization with the anti-id mAb MK2-23. The three patients developed anti-mouse IgG antibodies, anti-anti-id antibodies and anti-HMW-MAA antibodies. The anti-HMW-MAA antibodies are mainly IgG, suggesting that the immune response elicited by anti-id mAb MK2-23 is T-cell dependent. The development of anti-HMW-MAA immunity preceded the reduction in the size of metastatic lesions. This temporal relationship suggests but does not prove that the anti-HMW-MAA immunity elicited by anti-id mAb MK2-23 has a beneficial effect on the clinical course of the disease in patients with malignant melanoma. This finding in conjunction with minor side effects associated with repeated administrations of mouse anti-id mAb MK2-23 suggest that active specific immunotherapy with anti-id mAb which bear the Internal Image of melanoma-associated antigen represents a viable therapeutic approach to malignant melanoma.
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human high molecular weight melanoma associated antigen hmw maa mimicry by mouse anti idiotypic monoclonal antibody mk2 23 induction of humoral anti hmw maa immunity and prolongation of survival in patients with stage iv melanoma
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Abraham Mittelman, Z J Chen, Hong Yang, George Y Wong, Soldano FerroneAbstract:Abstract Twenty-five patients with stage IV melanoma were immunized with the mouse anti-idiotypic monoclonal antibody (mAb) MK2-23 (2 mg per injection), which bears the Internal Image of the determinant defined by anti-HMW-MAA mAb 763.74. Two patients were inevaluable, since they did not complete 4 weeks of therapy. Only 14 patients developed antibodies that were shown by serological and immunochemical assays to recognize the same or spatially close determinant as the anti-HMW-MAA mAb 763.74 and to express the idiotope defined by mAb MK2-23 in their antigen-combining sites. Side effects that are likely to be caused by bacillus Calmette-Guerin present in the immunogen consisted of erythema, induration, and ulceration at the sites of the injections. Occasionally, patients complained of flu-like symptoms, arthralgias, and myalgias. Three of the patients who developed anti-HMW-MAA antibodies achieved a partial response. It consisted of a decrease in the size of metastatic lesions and lasted 52 weeks in 1 patient and 93 weeks in the other 2 patients. Survival of the 14 patients who developed anti-HMW-MAA antibodies was significantly (P = 0.0003) longer than that of the 9 patients without detectable humoral anti-HMW-MAA immunity development. In the multivariate analysis, such an association between development of anti-HMW-MAA antibodies and survival prolongation was still significant (P = 0.001) after adjustment for difference in performance status, the only confounding factor found to be significantly related to survival. Lastly, a significant (P = 0.03 by likelihood ratio test) interaction between anti-HMW-MAA antibodies and patients' performance status was found, since the prolongation of survival associated with anti-HMW-MAA antibodies was more marked in patients with a performance status of less than or equal to 70% than in those with a higher one. These results suggest that anti-idiotypic mAb MK2-23 may represent a useful immunogen to implement active specific immunotherapy in patients with melanoma.
Berangere Avalle - One of the best experts on this subject based on the ideXlab platform.
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novel peptide inhibiting both tem 1 β lactamase and penicillin binding proteins
FEBS Journal, 2010Co-Authors: Denis Phichith, Jean-marie Frère, Moreno Galleni, Severine Padiolleaulefevre, Adeline Guellier, Soun Banh, Alain Friboulet, Daniel Thomas, Berangere AvalleAbstract:9G4H9, a catalytic antibody displaying β-lactamase-like activity, has been developed by the anti-idiotypic approach using β-lactamase as the first antigen. Thus 9G4H9 represents the ‘Internal Image‘ of β-lactamase. We selected a cyclic peptide anchored to a bacteriophage M13 library using 9G4H9 as the target. Pep90 is a cyclic heptapeptide enclosed between two cysteine residues. We showed that Pep90 could inhibit both TEM-1 β-lactamase (Ki = 333 μm) and several penicillin-binding proteins (IC50 values ranging from 6–62 μm). We determined that the tryptophan residue of Pep90 is of crucial importance for its inhibitory activity. Using Pep90 as a scaffold, we generated a new class of peptidomimetics that retained inhibitory activity towards TEM-1 β-lactamase.
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Enzyme mimicry by the antiidiotypic antibody approach
Proceedings of the National Academy of Sciences of the United States of America, 2000Co-Authors: Alexander V. Kolesnikov, Berangere Avalle, A. V. Kozyr, Elena Sergeevna Alexandrova, Frederic Koralewski, Alexander V. Demin, Mikhail I. Titov, Alfonso Tramontano, Sudhir Paul, Daniel ThomasAbstract:The concept of "Internal Image" of antiidiotypic antibodies has provided the basis for eliciting catalytic antibodies. A monoclonal IgM 9A8 that was obtained as an antiidiotype to AE-2 mAb, a known inhibitor of acetylcholinesterase, displayed esterolytic activity. Study of recombinant Fab fragments and separate light and heavy chains of 9A8 confirmed that the antibody variable domain encodes the catalytic function, whereas neither part of the primary sequence of the Fab exhibited homology with the enzyme. The specific modification of the 9A8 variable domain by an active site-directed covalent inhibitor revealed the presence of an active site Ser residue. A three-dimensional modeling suggests the existence of a functional catalytic dyad Ser-His. Comparison of active sites of 9A8 and 17E8 esterolytic abzyme raised against transition-state analog revealed structural similarity although both antibodies were elicited by two different approaches.
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functional mimicry elicitation of a monoclonal anti idiotypic antibody hydrolizing beta lactams
The FASEB Journal, 1998Co-Authors: Berangere Avalle, Daniel Thomas, Alain FribouletAbstract:Antigen mimicry by anti-idiotypic antibodies is investigated as a reliable strategy to achieve molecular imprinting of an enzymatic activity. A monoclonal anti-idiotypic antibody (Ab2-9G4H9) was elicited by using a monoclonal antibody (Ab1-7AF9) specific for the beta-lactamase active site. Catalytic features of Ab2 were characterized with beta-lactamase substrates. The antibody combining site appeared to have retained a part of the catalytic specificity. The relevance of the idiotypic mimicry concept for the generation of catalytic antibodies was further demonstrated by eliciting a third generation antibody (Ab3), which was shown to recognize beta-lactamase: the complete Internal Image properties of Ab2 9G4H9, including binding and catalytic properties, were thus checked.
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Abzyme generation using an anti-idiotypic antibody as the "Internal Image" of an enzyme active site.
Applied biochemistry and biotechnology, 1994Co-Authors: Alain Friboulet, L Izadyar, Berangere Avalle, A RosetoAbstract:Since the two reports published in 1986 by the laboratories of R. Lerner and P. G. Schultz, it has been clearly established that antibodies may be induced to act as catalysts in numerous chemical reactions. In all cases, catalytic antibodies were elicited using a substrate-based approach. In the present article, we propose an alternative and complementary enzyme-based approach to generate catalytic antibodies. This approach uses the properties of anti-idiotypic antibodies to generate Internal Images of enzyme active sites. Experimental results are discussed for polyclonal and monoclonal anti-idiotypic antibodies.