MMP-7 derived peptides with MHC class-I binding motifs from canine mammary tumor tissue elicit strong antigen-specific T-cell responses in BALB/c mice

Matrix Metalloproteinases (MMPs)-induced altered proteolysis of extracellular matrix proteins and basement membrane holds the key for tumor progression and metastasis. Matrix metalloproteinases-7 (Matrilysin), the smallest member of the MMP family also performs quite alike; thus serves as a potentia...

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Veröffentlicht in:Molecular and cellular biochemistry 2021-01, Vol.476 (1), p.311-320
Hauptverfasser: Yadav, Pavan Kumar, Gupta, Shishir Kumar, Kumar, Saroj, Ghosh, Mayukh, Yadav, Brijesh Singh, Kumar, Dinesh, Kumar, Ajay, Saini, Mohini, Kataria, Meena
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container_issue 1
container_start_page 311
container_title Molecular and cellular biochemistry
container_volume 476
creator Yadav, Pavan Kumar
Gupta, Shishir Kumar
Kumar, Saroj
Ghosh, Mayukh
Yadav, Brijesh Singh
Kumar, Dinesh
Kumar, Ajay
Saini, Mohini
Kataria, Meena
description Matrix Metalloproteinases (MMPs)-induced altered proteolysis of extracellular matrix proteins and basement membrane holds the key for tumor progression and metastasis. Matrix metalloproteinases-7 (Matrilysin), the smallest member of the MMP family also performs quite alike; thus serves as a potential candidate for anti-tumor immunotherapy. Conversely, being an endogenous tumor-associated antigen (TAA), targeting MMP-7 for immunization is challenging. But MMP-7-based xenovaccine can surmount the obstacle of poor immunogenicity and immunological tolerance, often encountered in TAA-based conventional vaccine for anti-tumor immunotherapy. This paves the way for investigating the potential of MMP-7-derived major histocompatibility complex (MHC)-binding peptides to elicit precise epitope-specific T-cell responses towards their possible inclusion in anti-tumor vaccine formulations. Perhaps it also ushers the path of achieving multiple epitope-based broad and universal cellular immunity. In current experiment, an immunoinformatics approach has been employed to identify the putative canine matrix matelloproteinases-7 (cMMP-7)-derived peptides with MHC class-I-binding motifs which can elicit potent antigen-specific immune responses in BALB/c mice. Immunization with the cMMP-7 DNA vaccine induced a strong CD8 + cytotoxic T lymphocytes (CTLs) and Th1- type response, with high level of gamma interferon (IFN-γ) production in BALB/c mice. The two identified putative MHC-I-binding nonameric peptides (Peptide 32-40 and Peptide 175-183 ) from cMMP-7 induced significant lymphocyte proliferation along with the production of IFN-γ from CD8 + T-cells in mice immunized with cMMP-7 DNA vaccine. The current observation has depicted the immunogenic potential of the two cMMP-7-derived nonapeptides for their possible exploitation in xenovaccine-mediated anti-tumor immunotherapy in mouse model.
doi_str_mv 10.1007/s11010-020-03908-2
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Matrix metalloproteinases-7 (Matrilysin), the smallest member of the MMP family also performs quite alike; thus serves as a potential candidate for anti-tumor immunotherapy. Conversely, being an endogenous tumor-associated antigen (TAA), targeting MMP-7 for immunization is challenging. But MMP-7-based xenovaccine can surmount the obstacle of poor immunogenicity and immunological tolerance, often encountered in TAA-based conventional vaccine for anti-tumor immunotherapy. This paves the way for investigating the potential of MMP-7-derived major histocompatibility complex (MHC)-binding peptides to elicit precise epitope-specific T-cell responses towards their possible inclusion in anti-tumor vaccine formulations. Perhaps it also ushers the path of achieving multiple epitope-based broad and universal cellular immunity. In current experiment, an immunoinformatics approach has been employed to identify the putative canine matrix matelloproteinases-7 (cMMP-7)-derived peptides with MHC class-I-binding motifs which can elicit potent antigen-specific immune responses in BALB/c mice. Immunization with the cMMP-7 DNA vaccine induced a strong CD8 + cytotoxic T lymphocytes (CTLs) and Th1- type response, with high level of gamma interferon (IFN-γ) production in BALB/c mice. The two identified putative MHC-I-binding nonameric peptides (Peptide 32-40 and Peptide 175-183 ) from cMMP-7 induced significant lymphocyte proliferation along with the production of IFN-γ from CD8 + T-cells in mice immunized with cMMP-7 DNA vaccine. The current observation has depicted the immunogenic potential of the two cMMP-7-derived nonapeptides for their possible exploitation in xenovaccine-mediated anti-tumor immunotherapy in mouse model.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-020-03908-2</identifier><identifier>PMID: 32970284</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Antigen (tumor-associated) ; Antigenic determinants ; Antigens ; Antigens, Neoplasm - metabolism ; Binding ; Biochemistry ; Biomedical and Life Sciences ; Breast cancer ; Cancer Vaccines ; Cardiology ; CD8 antigen ; Cell Line, Tumor ; Cell Proliferation ; Cell-mediated immunity ; Computational Biology ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; DNA vaccines ; Dogs ; Epitopes ; Epitopes - chemistry ; Extracellular matrix ; Female ; HEK293 Cells ; Histocompatibility Antigens Class I - immunology ; Humans ; Immune response ; Immunization ; Immunogenicity ; Immunoglobulin G - immunology ; Immunological tolerance ; Immunology ; Immunotherapy ; Immunotherapy - methods ; Interferon ; Interferon-gamma ; Life Sciences ; Lymphocyte Activation ; Lymphocytes ; Lymphocytes T ; Major histocompatibility complex ; Mammary gland ; Mammary Glands, Animal - metabolism ; Matrilysin ; Matrix metalloproteinase ; Matrix Metalloproteinase 7 - metabolism ; Matrix metalloproteinases ; Medical Biochemistry ; Metastases ; Mice ; Mice, Inbred BALB C ; Oncology ; Peptides ; Peptides - chemistry ; Protein Binding ; Proteolysis ; T cells ; T-Lymphocytes - cytology ; T-Lymphocytes - immunology ; T-Lymphocytes, Cytotoxic - immunology ; Tumors ; Vaccines ; γ-Interferon</subject><ispartof>Molecular and cellular biochemistry, 2021-01, Vol.476 (1), p.311-320</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>COPYRIGHT 2020 Springer</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-52f91ceaceb8278e064e69ab9f385e1e091c00dec9a0d8c4bc6e572c4e79a7123</citedby><cites>FETCH-LOGICAL-c541t-52f91ceaceb8278e064e69ab9f385e1e091c00dec9a0d8c4bc6e572c4e79a7123</cites><orcidid>0000-0002-1847-7486</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11010-020-03908-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11010-020-03908-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32970284$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yadav, Pavan Kumar</creatorcontrib><creatorcontrib>Gupta, Shishir Kumar</creatorcontrib><creatorcontrib>Kumar, Saroj</creatorcontrib><creatorcontrib>Ghosh, Mayukh</creatorcontrib><creatorcontrib>Yadav, Brijesh Singh</creatorcontrib><creatorcontrib>Kumar, Dinesh</creatorcontrib><creatorcontrib>Kumar, Ajay</creatorcontrib><creatorcontrib>Saini, Mohini</creatorcontrib><creatorcontrib>Kataria, Meena</creatorcontrib><title>MMP-7 derived peptides with MHC class-I binding motifs from canine mammary tumor tissue elicit strong antigen-specific T-cell responses in BALB/c mice</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><addtitle>Mol Cell Biochem</addtitle><description>Matrix Metalloproteinases (MMPs)-induced altered proteolysis of extracellular matrix proteins and basement membrane holds the key for tumor progression and metastasis. Matrix metalloproteinases-7 (Matrilysin), the smallest member of the MMP family also performs quite alike; thus serves as a potential candidate for anti-tumor immunotherapy. Conversely, being an endogenous tumor-associated antigen (TAA), targeting MMP-7 for immunization is challenging. But MMP-7-based xenovaccine can surmount the obstacle of poor immunogenicity and immunological tolerance, often encountered in TAA-based conventional vaccine for anti-tumor immunotherapy. This paves the way for investigating the potential of MMP-7-derived major histocompatibility complex (MHC)-binding peptides to elicit precise epitope-specific T-cell responses towards their possible inclusion in anti-tumor vaccine formulations. Perhaps it also ushers the path of achieving multiple epitope-based broad and universal cellular immunity. In current experiment, an immunoinformatics approach has been employed to identify the putative canine matrix matelloproteinases-7 (cMMP-7)-derived peptides with MHC class-I-binding motifs which can elicit potent antigen-specific immune responses in BALB/c mice. Immunization with the cMMP-7 DNA vaccine induced a strong CD8 + cytotoxic T lymphocytes (CTLs) and Th1- type response, with high level of gamma interferon (IFN-γ) production in BALB/c mice. The two identified putative MHC-I-binding nonameric peptides (Peptide 32-40 and Peptide 175-183 ) from cMMP-7 induced significant lymphocyte proliferation along with the production of IFN-γ from CD8 + T-cells in mice immunized with cMMP-7 DNA vaccine. 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In current experiment, an immunoinformatics approach has been employed to identify the putative canine matrix matelloproteinases-7 (cMMP-7)-derived peptides with MHC class-I-binding motifs which can elicit potent antigen-specific immune responses in BALB/c mice. Immunization with the cMMP-7 DNA vaccine induced a strong CD8 + cytotoxic T lymphocytes (CTLs) and Th1- type response, with high level of gamma interferon (IFN-γ) production in BALB/c mice. The two identified putative MHC-I-binding nonameric peptides (Peptide 32-40 and Peptide 175-183 ) from cMMP-7 induced significant lymphocyte proliferation along with the production of IFN-γ from CD8 + T-cells in mice immunized with cMMP-7 DNA vaccine. 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subjects Animals
Antigen (tumor-associated)
Antigenic determinants
Antigens
Antigens, Neoplasm - metabolism
Binding
Biochemistry
Biomedical and Life Sciences
Breast cancer
Cancer Vaccines
Cardiology
CD8 antigen
Cell Line, Tumor
Cell Proliferation
Cell-mediated immunity
Computational Biology
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA vaccines
Dogs
Epitopes
Epitopes - chemistry
Extracellular matrix
Female
HEK293 Cells
Histocompatibility Antigens Class I - immunology
Humans
Immune response
Immunization
Immunogenicity
Immunoglobulin G - immunology
Immunological tolerance
Immunology
Immunotherapy
Immunotherapy - methods
Interferon
Interferon-gamma
Life Sciences
Lymphocyte Activation
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Mammary gland
Mammary Glands, Animal - metabolism
Matrilysin
Matrix metalloproteinase
Matrix Metalloproteinase 7 - metabolism
Matrix metalloproteinases
Medical Biochemistry
Metastases
Mice
Mice, Inbred BALB C
Oncology
Peptides
Peptides - chemistry
Protein Binding
Proteolysis
T cells
T-Lymphocytes - cytology
T-Lymphocytes - immunology
T-Lymphocytes, Cytotoxic - immunology
Tumors
Vaccines
γ-Interferon
title MMP-7 derived peptides with MHC class-I binding motifs from canine mammary tumor tissue elicit strong antigen-specific T-cell responses in BALB/c mice
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T22%3A53%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MMP-7%20derived%20peptides%20with%20MHC%20class-I%20binding%20motifs%20from%20canine%20mammary%20tumor%20tissue%20elicit%20strong%20antigen-specific%20T-cell%20responses%20in%20BALB/c%20mice&rft.jtitle=Molecular%20and%20cellular%20biochemistry&rft.au=Yadav,%20Pavan%20Kumar&rft.date=2021-01-01&rft.volume=476&rft.issue=1&rft.spage=311&rft.epage=320&rft.pages=311-320&rft.issn=0300-8177&rft.eissn=1573-4919&rft_id=info:doi/10.1007/s11010-020-03908-2&rft_dat=%3Cgale_pubme%3EA651058465%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2486885407&rft_id=info:pmid/32970284&rft_galeid=A651058465&rfr_iscdi=true