The Experts below are selected from a list of 3360 Experts worldwide ranked by ideXlab platform
Erika Jensenjarolim - One of the best experts on this subject based on the ideXlab platform.
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Mimotope vaccination from allergy to cancer
Expert Opinion on Biological Therapy, 2009Co-Authors: Regina Knittelfelder, Angelika B. Riemer, Erika JensenjarolimAbstract:Background: Mimotopes are peptides mimicking protein, carbohydrates or lipid epitopes and can be generated by phage display technology. When selected by antibodies, they represent exclusively B-cell epitopes and are devoid of antigen/allergen-specific T-cell epitopes. Coupled to carriers or presented in a multiple antigenic peptide form Mimotopes achieve immunogenicity and induce epitope-specific antibody responses upon vaccination. Objective/methods: In allergy IgG antibodies may block IgE binding to allergens, whereas other IgG antibody specificities enhance this and support the anaphylactic reaction. In cancer, inhibitory antibody specificities prevent growth signals derived from overexpressed oncogenes, whereas growth-promoting specificities enhance signalling and proliferation. Therefore, the Mimotope concept is applicable to both fields for epitope-specific vaccination and analysis of conformational B-cell epitopes for the allergen/antigen. Results/conclusions: Mimotope technology is a relatively yo...
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vaccination strategies based on the Mimotope concept
Giornale italiano di dermatologia e venereologia : organo ufficiale Società italiana di dermatologia e sifilografia, 2008Co-Authors: Krisztina Szalai, Erika Jensenjarolim, Isabella PalischollAbstract:: Specific immunotherapies are in broad use for many diseases like allergies, cancer, autoimmune diseases or parasitic infections. Although clinical trials show successful application of these therapies, several disadvantages hinder the complete success. High production costs and repeated administrations represent the practical problems, while the possibly occurring side effects are the therapeutic troubles. To avoid these problems, the target specificity should be considered more intensely. Epitopes, the particular parts of antigens/allergens where they bind specific antibodies, are useful targets. To generate an epitope-specific vaccination, Mimotopes can be identified via the biopanning technology. Mimotopes are small peptides mimicking the epitopes in the structural as well as in the immunological point of few. They are able to induce antigen-specific antibodies in active immunization form. These antibodies are directed against the natural antigen/allergen, and therefore they are able to block the outbreak of the diseases. Current research focuses on the development of Mimotopes to achieve an epitope-specific induction of blocking antibodies, e.g. for allergy treatment. In cancer therapy, studies with Mimotopes show successful interference with tumor cell growth in immunizations of mice. Also in the case of autoimmune diseases and parasitic infections this method was applied, targeting different molecules, which are key mediators in the disease mechanisms. Through the Mimotope treatment via the specific antibody production, the disease symptoms could be hampered. This review gives an overview of the use of the Mimotope concept and also of related therapeutic trials for the treatment of allergy, cancer, autoimmune and infectious diseases.
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Mimotope vaccines epitope mimics induce anti cancer antibodies
Immunology Letters, 2007Co-Authors: Angelika B. Riemer, Erika JensenjarolimAbstract:Mimotopes are epitope-mimicking structures. When applied for immunizations they induce desired antibody specificities exclusively based on the principle of molecular mimicry. This is important as antibodies directed against tumor-associated antigens may harbor diverse biological effects depending on their epitope specificity. Thus they may inhibit or promote tumor growth. This review gives an update on different vaccination strategies based on the Mimotope concept.
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active induction of tumor specific ige antibodies by oral Mimotope vaccination
Cancer Research, 2007Co-Authors: Angelika B. Riemer, Otto Scheiner, Christoph C Zielinski, Regina Knittelfelder, Eva Untersmayr, H Pehamberger, Albert Duschl, Erika JensenjarolimAbstract:A role of IgE antibodies in cancer surveillance has been implicated for a long time. Studies dealing with IgE antibodies directly targeted to tumor antigens have shown marked anticancer effects mediated by this antibody class. Thus, the basic function of IgE antibodies may be to control tumor growth. Thus far, cancer-specific IgE has only been applied passively. Consequently, the aim of this study was to establish an active vaccination protocol to induce tumor antigen-specific IgE antibodies, and to evaluate functional properties. We previously generated epitope mimics, so-called Mimotopes, for the epitope recognized by the anti-HER-2 antibody trastuzumab. Upon i.p. immunizations, IgG antibodies with trastuzumab-like properties could be elicited. In the present study, we immunized BALB/c mice via the oral route with these trastuzumab Mimotopes, under simultaneous neutralization and suppression of gastric acid. As shown in preceding experiments, this feeding regimen effectively induces Th2 immune responses. Oral immunizations with trastuzumab Mimotopes under hypoacidic conditions indeed resulted in the formation of IgE antibodies towards the HER-2 antigen. Moreover, anti-HER-2 IgE-sensitized effector cells mediated SK-BR-3 target cell lysis in an antibody-dependent cytotoxicity assay. We conclude that directed and epitope-specific induction of IgE against tumor antigens is feasible with an oral Mimotope vaccination regimen, and that these antibodies mediate anticancer effects.
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high molecular weight melanoma associated antigen Mimotope immunizations induce antibodies recognizing melanoma cells
Cancer Immunology Immunotherapy, 2005Co-Authors: Angelika B. Riemer, Georg Kraml, Otto Scheiner, Christoph C Zielinski, Brigitte Hantusch, Barbara Sponer, Christine Hafner, H Pehamberger, Erika JensenjarolimAbstract:Size and posttranslational modifications are obstacles in the recombinant expression of high-molecular-weight melanoma-associated antigen (HMW-MAA). Creating a tumor antigen mimic via the phage display technology may be a means to overcome this problem for vaccine design. In this study, we aimed to generate an immunogenic epitope mimic of HMW-MAA. Therefore we screened a linear 9mer phage display peptide library, using the anti-HMW-MAA monoclonal antibody (mAb) 225.28S. This antibody mediates antibody-dependent cellular cytotoxicity (ADCC) and has already been used for anti-idiotype therapy trials. Fifteen peptides were selected by mAb 225.28S in the biopanning procedure. They share a consensus sequence, but show only partial homology to the amino acid sequence of the HMW-MAA core protein, indicating mimicry with a conformational epitope. One Mimotope was chosen to be fused to albumin binding protein (ABP) as an immunogenic carrier. Immunoassays with 225.28S indicated that the Mimotope fusion protein was folded correctly. Subsequently, the fusion protein was tested for immunogenicity in BALB/c mice. The induced anti-Mimotope antibodies recognized HMW-MAA of 518A2 human melanoma cells, whereas sera of mice immunized with the carrier ABP alone showed no reactivity. These anti-Mimotope antibodies were capable of inducing specific lysis of 518A2 melanoma cells in ADCC assays with murine effector cells. In conclusion, the presented data indicate that Mimotopes fused to an immunogenic carrier are suitable tools to elicit epitope-specific anti-melanoma immune responses.
Otto Scheiner - One of the best experts on this subject based on the ideXlab platform.
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specificity of Mimotope induced anti high molecular weight melanoma associated antigen hmw maa antibodies does not ensure biological activity
PLOS ONE, 2011Co-Authors: Julia Latzka, Otto Scheiner, Heimo Breiteneder, Sonja Gaier, Gerlinde Hofstetter, Nina Balazs, Ursula Smole, Soldano Ferrone, H Pehamberger, Stefan WagnerAbstract:Vaccines based on peptide mimics (Mimotopes) of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a Mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA) that elicited HMW-MAA-specific antibodies (Abs) with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify Mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polyMimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs) VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH), both HMW-MAA Mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the Mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate Mimotopes of the corresponding epitopes.
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active induction of tumor specific ige antibodies by oral Mimotope vaccination
Cancer Research, 2007Co-Authors: Angelika B. Riemer, Otto Scheiner, Christoph C Zielinski, Regina Knittelfelder, Eva Untersmayr, H Pehamberger, Albert Duschl, Erika JensenjarolimAbstract:A role of IgE antibodies in cancer surveillance has been implicated for a long time. Studies dealing with IgE antibodies directly targeted to tumor antigens have shown marked anticancer effects mediated by this antibody class. Thus, the basic function of IgE antibodies may be to control tumor growth. Thus far, cancer-specific IgE has only been applied passively. Consequently, the aim of this study was to establish an active vaccination protocol to induce tumor antigen-specific IgE antibodies, and to evaluate functional properties. We previously generated epitope mimics, so-called Mimotopes, for the epitope recognized by the anti-HER-2 antibody trastuzumab. Upon i.p. immunizations, IgG antibodies with trastuzumab-like properties could be elicited. In the present study, we immunized BALB/c mice via the oral route with these trastuzumab Mimotopes, under simultaneous neutralization and suppression of gastric acid. As shown in preceding experiments, this feeding regimen effectively induces Th2 immune responses. Oral immunizations with trastuzumab Mimotopes under hypoacidic conditions indeed resulted in the formation of IgE antibodies towards the HER-2 antigen. Moreover, anti-HER-2 IgE-sensitized effector cells mediated SK-BR-3 target cell lysis in an antibody-dependent cytotoxicity assay. We conclude that directed and epitope-specific induction of IgE against tumor antigens is feasible with an oral Mimotope vaccination regimen, and that these antibodies mediate anticancer effects.
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Mimotopes identify conformational epitopes on parvalbumin, the major fish allergen
Molecular Immunology, 2005Co-Authors: Eva Untersmayr, Angelika B. Riemer, Otto Scheiner, Brigitte Hantusch, Isabella Schöll, Krisztina Szalai, Wolfgang Hemmer, Ines Swoboda, Susanne Spitzauer, Reinhart JarischAbstract:Abstract Parvalbumin, the major fish allergen, is recognized by allergen-specific IgE of more than 90% of all fish-allergic patients. A detailed knowledge of allergenic structures is crucial for developing a vaccine inducing blocking antibodies specifically directed towards the IgE binding epitopes. In the present study we aimed to use the phage display technique to generate Mimotopes, which mimic epitopes on parvalbumin. Parvalbumin-specific IgE was purified from sera of fish-allergic patients and used for screening of a constrained decamer phage library. After four rounds of biopanning using parvalbumin-specific IgE, five phage clones were selected which were specifically recognized by parvalbumin-specific IgE as well as IgG. DNA sequencing and peptide alignment revealed a high degree of sequence similarities between the Mimotopes. Interestingly, on the surface of natural parvalbumin three regions could be defined by computational Mimotope matching. In accordance, previously defined allergenic peptides of cod parvalbumin highlighted areas in close proximity or overlapping with the Mimotope matching sites. From the presented data we conclude that our approach identified conformational epitopes of parvalbumin relevant for IgE and IgG binding. We suggest that these Mimotopes are suitable candidates for an epitope-specific immunotherapy of fish-allergic patients.
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high molecular weight melanoma associated antigen Mimotope immunizations induce antibodies recognizing melanoma cells
Cancer Immunology Immunotherapy, 2005Co-Authors: Angelika B. Riemer, Georg Kraml, Otto Scheiner, Christoph C Zielinski, Brigitte Hantusch, Barbara Sponer, Christine Hafner, H Pehamberger, Erika JensenjarolimAbstract:Size and posttranslational modifications are obstacles in the recombinant expression of high-molecular-weight melanoma-associated antigen (HMW-MAA). Creating a tumor antigen mimic via the phage display technology may be a means to overcome this problem for vaccine design. In this study, we aimed to generate an immunogenic epitope mimic of HMW-MAA. Therefore we screened a linear 9mer phage display peptide library, using the anti-HMW-MAA monoclonal antibody (mAb) 225.28S. This antibody mediates antibody-dependent cellular cytotoxicity (ADCC) and has already been used for anti-idiotype therapy trials. Fifteen peptides were selected by mAb 225.28S in the biopanning procedure. They share a consensus sequence, but show only partial homology to the amino acid sequence of the HMW-MAA core protein, indicating mimicry with a conformational epitope. One Mimotope was chosen to be fused to albumin binding protein (ABP) as an immunogenic carrier. Immunoassays with 225.28S indicated that the Mimotope fusion protein was folded correctly. Subsequently, the fusion protein was tested for immunogenicity in BALB/c mice. The induced anti-Mimotope antibodies recognized HMW-MAA of 518A2 human melanoma cells, whereas sera of mice immunized with the carrier ABP alone showed no reactivity. These anti-Mimotope antibodies were capable of inducing specific lysis of 518A2 melanoma cells in ADCC assays with murine effector cells. In conclusion, the presented data indicate that Mimotopes fused to an immunogenic carrier are suitable tools to elicit epitope-specific anti-melanoma immune responses.
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vaccination with a human high molecular weight melanoma associated antigen Mimotope induces a humoral response inhibiting melanoma cell growth in vitro
Journal of Immunology, 2005Co-Authors: Stefan Wagner, Otto Scheiner, Christoph C Zielinski, Ursula Wiedermann, Christine Hafner, Soldano Ferrone, H Pehamberger, Joanna Jasinska, Dorothee Allwardt, Heimo BreitenederAbstract:Peptide mimics of a conformational epitope that is recognized by a mAb with antitumor activity are promising candidates for formulations of anticancer vaccines. These Mimotope vaccines are able to induce a polyclonal Ab response focused to the determinant of the mAb. Such attempts at cancer immunotherapy are of special interest for malignant melanoma that is highly resistant to chemotherapy and radiotherapy. In this study, we describe for the first time the design and immunogenicity of a vaccine containing a Mimotope of the human high m.w. melanoma-associated Ag (HMW-MAA) and the biological potential of the induced Abs. Mimotopes were selected from a pVIII-9mer phage display peptide library with the anti-HMW-MAA mAb 225.28S. The Mimotope vaccine was then generated by coupling the most suitable candidate Mimotope to tetanus toxoid as an immunogenic carrier. Immunization of rabbits with this vaccine induced a specific humoral immune response directed toward the epitope recognized by the mAb 225.28S on the native HMW-MAA. The induced Abs inhibited the in vitro growth of the melanoma cell line 518A2 up to 62%. In addition, the Abs mediated 26% lysis of 518A2 cells in Ab-dependent cellular cytotoxicity. Our results indicate a possible application of this Mimotope vaccine as a novel immunotherapeutic agent for the treatment of malignant melanoma.
Angelika B. Riemer - One of the best experts on this subject based on the ideXlab platform.
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Mimotope vaccination from allergy to cancer
Expert Opinion on Biological Therapy, 2009Co-Authors: Regina Knittelfelder, Angelika B. Riemer, Erika JensenjarolimAbstract:Background: Mimotopes are peptides mimicking protein, carbohydrates or lipid epitopes and can be generated by phage display technology. When selected by antibodies, they represent exclusively B-cell epitopes and are devoid of antigen/allergen-specific T-cell epitopes. Coupled to carriers or presented in a multiple antigenic peptide form Mimotopes achieve immunogenicity and induce epitope-specific antibody responses upon vaccination. Objective/methods: In allergy IgG antibodies may block IgE binding to allergens, whereas other IgG antibody specificities enhance this and support the anaphylactic reaction. In cancer, inhibitory antibody specificities prevent growth signals derived from overexpressed oncogenes, whereas growth-promoting specificities enhance signalling and proliferation. Therefore, the Mimotope concept is applicable to both fields for epitope-specific vaccination and analysis of conformational B-cell epitopes for the allergen/antigen. Results/conclusions: Mimotope technology is a relatively yo...
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Mimotope vaccination – from allergy to cancer
Expert Opinion on Biological Therapy, 2009Co-Authors: Regina Knittelfelder, Angelika B. Riemer, Erika Jensen-jarolimAbstract:Background: Mimotopes are peptides mimicking protein, carbohydrates or lipid epitopes and can be generated by phage display technology. When selected by antibodies, they represent exclusively B-cell epitopes and are devoid of antigen/allergen-specific T-cell epitopes. Coupled to carriers or presented in a multiple antigenic peptide form Mimotopes achieve immunogenicity and induce epitope-specific antibody responses upon vaccination. Objective/methods: In allergy IgG antibodies may block IgE binding to allergens, whereas other IgG antibody specificities enhance this and support the anaphylactic reaction. In cancer, inhibitory antibody specificities prevent growth signals derived from overexpressed oncogenes, whereas growth-promoting specificities enhance signalling and proliferation. Therefore, the Mimotope concept is applicable to both fields for epitope-specific vaccination and analysis of conformational B-cell epitopes for the allergen/antigen. Results/conclusions: Mimotope technology is a relatively yo...
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Mimotope vaccines epitope mimics induce anti cancer antibodies
Immunology Letters, 2007Co-Authors: Angelika B. Riemer, Erika JensenjarolimAbstract:Mimotopes are epitope-mimicking structures. When applied for immunizations they induce desired antibody specificities exclusively based on the principle of molecular mimicry. This is important as antibodies directed against tumor-associated antigens may harbor diverse biological effects depending on their epitope specificity. Thus they may inhibit or promote tumor growth. This review gives an update on different vaccination strategies based on the Mimotope concept.
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active induction of tumor specific ige antibodies by oral Mimotope vaccination
Cancer Research, 2007Co-Authors: Angelika B. Riemer, Otto Scheiner, Christoph C Zielinski, Regina Knittelfelder, Eva Untersmayr, H Pehamberger, Albert Duschl, Erika JensenjarolimAbstract:A role of IgE antibodies in cancer surveillance has been implicated for a long time. Studies dealing with IgE antibodies directly targeted to tumor antigens have shown marked anticancer effects mediated by this antibody class. Thus, the basic function of IgE antibodies may be to control tumor growth. Thus far, cancer-specific IgE has only been applied passively. Consequently, the aim of this study was to establish an active vaccination protocol to induce tumor antigen-specific IgE antibodies, and to evaluate functional properties. We previously generated epitope mimics, so-called Mimotopes, for the epitope recognized by the anti-HER-2 antibody trastuzumab. Upon i.p. immunizations, IgG antibodies with trastuzumab-like properties could be elicited. In the present study, we immunized BALB/c mice via the oral route with these trastuzumab Mimotopes, under simultaneous neutralization and suppression of gastric acid. As shown in preceding experiments, this feeding regimen effectively induces Th2 immune responses. Oral immunizations with trastuzumab Mimotopes under hypoacidic conditions indeed resulted in the formation of IgE antibodies towards the HER-2 antigen. Moreover, anti-HER-2 IgE-sensitized effector cells mediated SK-BR-3 target cell lysis in an antibody-dependent cytotoxicity assay. We conclude that directed and epitope-specific induction of IgE against tumor antigens is feasible with an oral Mimotope vaccination regimen, and that these antibodies mediate anticancer effects.
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Mimotopes identify conformational epitopes on parvalbumin, the major fish allergen
Molecular Immunology, 2005Co-Authors: Eva Untersmayr, Angelika B. Riemer, Otto Scheiner, Brigitte Hantusch, Isabella Schöll, Krisztina Szalai, Wolfgang Hemmer, Ines Swoboda, Susanne Spitzauer, Reinhart JarischAbstract:Abstract Parvalbumin, the major fish allergen, is recognized by allergen-specific IgE of more than 90% of all fish-allergic patients. A detailed knowledge of allergenic structures is crucial for developing a vaccine inducing blocking antibodies specifically directed towards the IgE binding epitopes. In the present study we aimed to use the phage display technique to generate Mimotopes, which mimic epitopes on parvalbumin. Parvalbumin-specific IgE was purified from sera of fish-allergic patients and used for screening of a constrained decamer phage library. After four rounds of biopanning using parvalbumin-specific IgE, five phage clones were selected which were specifically recognized by parvalbumin-specific IgE as well as IgG. DNA sequencing and peptide alignment revealed a high degree of sequence similarities between the Mimotopes. Interestingly, on the surface of natural parvalbumin three regions could be defined by computational Mimotope matching. In accordance, previously defined allergenic peptides of cod parvalbumin highlighted areas in close proximity or overlapping with the Mimotope matching sites. From the presented data we conclude that our approach identified conformational epitopes of parvalbumin relevant for IgE and IgG binding. We suggest that these Mimotopes are suitable candidates for an epitope-specific immunotherapy of fish-allergic patients.
H Pehamberger - One of the best experts on this subject based on the ideXlab platform.
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specificity of Mimotope induced anti high molecular weight melanoma associated antigen hmw maa antibodies does not ensure biological activity
PLOS ONE, 2011Co-Authors: Julia Latzka, Otto Scheiner, Heimo Breiteneder, Sonja Gaier, Gerlinde Hofstetter, Nina Balazs, Ursula Smole, Soldano Ferrone, H Pehamberger, Stefan WagnerAbstract:Vaccines based on peptide mimics (Mimotopes) of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a Mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA) that elicited HMW-MAA-specific antibodies (Abs) with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify Mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polyMimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs) VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH), both HMW-MAA Mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the Mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate Mimotopes of the corresponding epitopes.
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active induction of tumor specific ige antibodies by oral Mimotope vaccination
Cancer Research, 2007Co-Authors: Angelika B. Riemer, Otto Scheiner, Christoph C Zielinski, Regina Knittelfelder, Eva Untersmayr, H Pehamberger, Albert Duschl, Erika JensenjarolimAbstract:A role of IgE antibodies in cancer surveillance has been implicated for a long time. Studies dealing with IgE antibodies directly targeted to tumor antigens have shown marked anticancer effects mediated by this antibody class. Thus, the basic function of IgE antibodies may be to control tumor growth. Thus far, cancer-specific IgE has only been applied passively. Consequently, the aim of this study was to establish an active vaccination protocol to induce tumor antigen-specific IgE antibodies, and to evaluate functional properties. We previously generated epitope mimics, so-called Mimotopes, for the epitope recognized by the anti-HER-2 antibody trastuzumab. Upon i.p. immunizations, IgG antibodies with trastuzumab-like properties could be elicited. In the present study, we immunized BALB/c mice via the oral route with these trastuzumab Mimotopes, under simultaneous neutralization and suppression of gastric acid. As shown in preceding experiments, this feeding regimen effectively induces Th2 immune responses. Oral immunizations with trastuzumab Mimotopes under hypoacidic conditions indeed resulted in the formation of IgE antibodies towards the HER-2 antigen. Moreover, anti-HER-2 IgE-sensitized effector cells mediated SK-BR-3 target cell lysis in an antibody-dependent cytotoxicity assay. We conclude that directed and epitope-specific induction of IgE against tumor antigens is feasible with an oral Mimotope vaccination regimen, and that these antibodies mediate anticancer effects.
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high molecular weight melanoma associated antigen Mimotope immunizations induce antibodies recognizing melanoma cells
Cancer Immunology Immunotherapy, 2005Co-Authors: Angelika B. Riemer, Georg Kraml, Otto Scheiner, Christoph C Zielinski, Brigitte Hantusch, Barbara Sponer, Christine Hafner, H Pehamberger, Erika JensenjarolimAbstract:Size and posttranslational modifications are obstacles in the recombinant expression of high-molecular-weight melanoma-associated antigen (HMW-MAA). Creating a tumor antigen mimic via the phage display technology may be a means to overcome this problem for vaccine design. In this study, we aimed to generate an immunogenic epitope mimic of HMW-MAA. Therefore we screened a linear 9mer phage display peptide library, using the anti-HMW-MAA monoclonal antibody (mAb) 225.28S. This antibody mediates antibody-dependent cellular cytotoxicity (ADCC) and has already been used for anti-idiotype therapy trials. Fifteen peptides were selected by mAb 225.28S in the biopanning procedure. They share a consensus sequence, but show only partial homology to the amino acid sequence of the HMW-MAA core protein, indicating mimicry with a conformational epitope. One Mimotope was chosen to be fused to albumin binding protein (ABP) as an immunogenic carrier. Immunoassays with 225.28S indicated that the Mimotope fusion protein was folded correctly. Subsequently, the fusion protein was tested for immunogenicity in BALB/c mice. The induced anti-Mimotope antibodies recognized HMW-MAA of 518A2 human melanoma cells, whereas sera of mice immunized with the carrier ABP alone showed no reactivity. These anti-Mimotope antibodies were capable of inducing specific lysis of 518A2 melanoma cells in ADCC assays with murine effector cells. In conclusion, the presented data indicate that Mimotopes fused to an immunogenic carrier are suitable tools to elicit epitope-specific anti-melanoma immune responses.
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vaccination with a human high molecular weight melanoma associated antigen Mimotope induces a humoral response inhibiting melanoma cell growth in vitro
Journal of Immunology, 2005Co-Authors: Stefan Wagner, Otto Scheiner, Christoph C Zielinski, Ursula Wiedermann, Christine Hafner, Soldano Ferrone, H Pehamberger, Joanna Jasinska, Dorothee Allwardt, Heimo BreitenederAbstract:Peptide mimics of a conformational epitope that is recognized by a mAb with antitumor activity are promising candidates for formulations of anticancer vaccines. These Mimotope vaccines are able to induce a polyclonal Ab response focused to the determinant of the mAb. Such attempts at cancer immunotherapy are of special interest for malignant melanoma that is highly resistant to chemotherapy and radiotherapy. In this study, we describe for the first time the design and immunogenicity of a vaccine containing a Mimotope of the human high m.w. melanoma-associated Ag (HMW-MAA) and the biological potential of the induced Abs. Mimotopes were selected from a pVIII-9mer phage display peptide library with the anti-HMW-MAA mAb 225.28S. The Mimotope vaccine was then generated by coupling the most suitable candidate Mimotope to tetanus toxoid as an immunogenic carrier. Immunization of rabbits with this vaccine induced a specific humoral immune response directed toward the epitope recognized by the mAb 225.28S on the native HMW-MAA. The induced Abs inhibited the in vitro growth of the melanoma cell line 518A2 up to 62%. In addition, the Abs mediated 26% lysis of 518A2 cells in Ab-dependent cellular cytotoxicity. Our results indicate a possible application of this Mimotope vaccine as a novel immunotherapeutic agent for the treatment of malignant melanoma.
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epitope specific antibody response to mel cam induced by Mimotope immunization
Journal of Investigative Dermatology, 2005Co-Authors: Christine Hafner, Otto Scheiner, Ursula Wiedermann, H Pehamberger, Stefan Wagner, Joanna Jasinska, Dorothee Allwardt, Klaus Wolff, Heimo BreitenederAbstract:Peptide Mimotopes of tumor antigen epitopes have been proposed as components of tumor vaccines. In this study, we determined the immunogenicity of melcam mim1 and melcam mim2, peptide mimics of an epitope of the melanoma cell-adhesion molecule (Mel-CAM). BALB/c mice were vaccinated either with Mimotopes or Mimotopes coupled to tetanus toxoid (TT). The antibody responses of mice to melcam mim1, melcam mim2, and recombinant Mel-CAM were analyzed by an ELISA and immunoblot analyses. TT-coupled Mimotopes led to high titers of IgG mainly of the IgG2a subclass to melcam mim1 and melcam mim2. Immunization with each of the Mimotope formulations induced antibodies that cross-reacted with recombinant Mel-CAM. Uncoupled Mimotopes induced lymphocyte proliferation and cytokine production in spleen cell cultures indicating that both peptide Mimotopes also contained T cell epitopes. TT-coupled Mimotopes induced T helper (Th)1 (interleukin (IL)-2, interferon-γ) and Th2 (IL-4, IL-5) cytokines, whereas uncoupled Mimotopes induced a Th1-biased T cell response. Our results suggest that Mimotopes potentially represent a novel vaccine approach to induce a tumor antigen-specific humoral and cellular response.
Heimo Breiteneder - One of the best experts on this subject based on the ideXlab platform.
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specificity of Mimotope induced anti high molecular weight melanoma associated antigen hmw maa antibodies does not ensure biological activity
PLOS ONE, 2011Co-Authors: Julia Latzka, Otto Scheiner, Heimo Breiteneder, Sonja Gaier, Gerlinde Hofstetter, Nina Balazs, Ursula Smole, Soldano Ferrone, H Pehamberger, Stefan WagnerAbstract:Vaccines based on peptide mimics (Mimotopes) of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a Mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA) that elicited HMW-MAA-specific antibodies (Abs) with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify Mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polyMimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs) VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH), both HMW-MAA Mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the Mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate Mimotopes of the corresponding epitopes.
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vaccination with a human high molecular weight melanoma associated antigen Mimotope induces a humoral response inhibiting melanoma cell growth in vitro
Journal of Immunology, 2005Co-Authors: Stefan Wagner, Otto Scheiner, Christoph C Zielinski, Ursula Wiedermann, Christine Hafner, Soldano Ferrone, H Pehamberger, Joanna Jasinska, Dorothee Allwardt, Heimo BreitenederAbstract:Peptide mimics of a conformational epitope that is recognized by a mAb with antitumor activity are promising candidates for formulations of anticancer vaccines. These Mimotope vaccines are able to induce a polyclonal Ab response focused to the determinant of the mAb. Such attempts at cancer immunotherapy are of special interest for malignant melanoma that is highly resistant to chemotherapy and radiotherapy. In this study, we describe for the first time the design and immunogenicity of a vaccine containing a Mimotope of the human high m.w. melanoma-associated Ag (HMW-MAA) and the biological potential of the induced Abs. Mimotopes were selected from a pVIII-9mer phage display peptide library with the anti-HMW-MAA mAb 225.28S. The Mimotope vaccine was then generated by coupling the most suitable candidate Mimotope to tetanus toxoid as an immunogenic carrier. Immunization of rabbits with this vaccine induced a specific humoral immune response directed toward the epitope recognized by the mAb 225.28S on the native HMW-MAA. The induced Abs inhibited the in vitro growth of the melanoma cell line 518A2 up to 62%. In addition, the Abs mediated 26% lysis of 518A2 cells in Ab-dependent cellular cytotoxicity. Our results indicate a possible application of this Mimotope vaccine as a novel immunotherapeutic agent for the treatment of malignant melanoma.
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epitope specific antibody response to mel cam induced by Mimotope immunization
Journal of Investigative Dermatology, 2005Co-Authors: Christine Hafner, Otto Scheiner, Ursula Wiedermann, H Pehamberger, Stefan Wagner, Joanna Jasinska, Dorothee Allwardt, Klaus Wolff, Heimo BreitenederAbstract:Peptide Mimotopes of tumor antigen epitopes have been proposed as components of tumor vaccines. In this study, we determined the immunogenicity of melcam mim1 and melcam mim2, peptide mimics of an epitope of the melanoma cell-adhesion molecule (Mel-CAM). BALB/c mice were vaccinated either with Mimotopes or Mimotopes coupled to tetanus toxoid (TT). The antibody responses of mice to melcam mim1, melcam mim2, and recombinant Mel-CAM were analyzed by an ELISA and immunoblot analyses. TT-coupled Mimotopes led to high titers of IgG mainly of the IgG2a subclass to melcam mim1 and melcam mim2. Immunization with each of the Mimotope formulations induced antibodies that cross-reacted with recombinant Mel-CAM. Uncoupled Mimotopes induced lymphocyte proliferation and cytokine production in spleen cell cultures indicating that both peptide Mimotopes also contained T cell epitopes. TT-coupled Mimotopes induced T helper (Th)1 (interleukin (IL)-2, interferon-γ) and Th2 (IL-4, IL-5) cytokines, whereas uncoupled Mimotopes induced a Th1-biased T cell response. Our results suggest that Mimotopes potentially represent a novel vaccine approach to induce a tumor antigen-specific humoral and cellular response.
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Monovalent fusion proteins of IgE Mimotopes are safe for therapy of type I allergy
The FASEB Journal, 2001Co-Authors: Erika Ganglberger, Barbara Sponer, Isabella Schöll, Ursula Wiedermann, Sigrid Baumann, Christine Hafner, Heimo Breiteneder, Mark Suter, George Boltz-nitulescu, Otto ScheinerAbstract:By screening phage display random peptide libraries with purified immunoglobulin E (IgE) from birch pollen-allergic patients, we previously defined peptides mimicking natural IgE epitopes (Mimotopes) of the major birch pollen allergen Bet v 1. The present study aimed to define a monovalent carrier for the IgE Mimotopes to i nduce protective antibodies directed to the IgE epitopes, suitable for Mimotope-specific therapy. We expressed the selected Mimotopes as fusion proteins together with streptococcal albumin binding protein (ABP). The fusion proteins were recognized specifically by anti- Bet v 1 human IgE, which demonstrated that the Mimotopes fused to ABP resemble the natural IgE epitope. Bet v 1-specific IgG was induced by immunization of BALB/c mice with fusion proteins. These IgG antibodies could inhibit IgE binding to Bet v 1. Skin testing of Bet v 1 allergic mice showed that the ABP Mimotope constructs did not elicit type I skin reactions, although they possess IgE bindi ng structures. Our data suggest that IgE Mimotopes are safe for epitope-specific immunotherapy of sensitized individuals, when presented in a monovalent form. Therefore, ABP-fused Mimotopes are promising candidates for a new type of immunotherapy based on the precise induction of blocking antibodies.
