Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma
The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC). This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containin...
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| Veröffentlicht in: | Journal of immunotherapy (1997) 2011-06, Vol.34 (5), p.448-456 |
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| creator | WILGENHOF, Sofie VAN NUFFEL, An M. T BONEHILL, Aude THIELEMANS, Kris NEYNS, Bart CORTHALS, Jurgen HEIRMAN, Carlo TUYAERTS, Sandra BENTEYN, Daphné DE CONINCK, Arlette VAN RIET, Ivan VERFAILLIE, Guy VANDELOO, Judith |
| description | The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC). This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containing autologous TriMix-DC co-electroporated with mRNA encoding a human leukocyte antigen class II-targeting signal linked to 1 of 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, and gp100) in patients with advanced melanoma. Thirty-five American Joint Committee on Cancer stage III/IV melanoma patients received autologous TriMix-DC (4 administrations 2 weeks apart). Immune monitoring was performed by evaluating skin biopsies of delayed type IV hypersensitivity (DTH) reactions for presence of vaccinal antigen-specific DTH-infiltrating lymphocytes (DIL). Thereafter, patients could receive interferon-alpha-2b (IFN-α-2b) 5 MU subcutaneously 3 times weekly and additional TriMix-DC every 8 weeks. TriMix-DC-related adverse events comprised grade 2 local injection site reactions (all patients), and grade 2 fever and lethargy (2 patients). Vaccinal antigen-specific DIL were found in 0/6 patients tested at vaccine initiation and in 12/21 (57.1%) assessed after the fourth vaccine. A positive postvaccination DTH test correlated with IL-12p70 secretion capacity of TriMix-DC. No objective responses to TriMix-DC alone were seen according to RECIST. Twenty-nine patients received IFN-α-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-α-2b combination therapy, 1 partial response and 5 stable disease (disease control of >6 months with regression of metastases) were observed in 17 patients with evaluable disease at baseline. In conclusion, this study demonstrated that therapeutic vaccination with autologous TriMix-DC is feasible, safe, and immunogenic and can be combined with sequential IFN-α-2b. |
| doi_str_mv | 10.1097/CJI.0b013e31821dcb31 |
| format | Article |
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T ; BONEHILL, Aude ; THIELEMANS, Kris ; NEYNS, Bart ; CORTHALS, Jurgen ; HEIRMAN, Carlo ; TUYAERTS, Sandra ; BENTEYN, Daphné ; DE CONINCK, Arlette ; VAN RIET, Ivan ; VERFAILLIE, Guy ; VANDELOO, Judith</creator><creatorcontrib>WILGENHOF, Sofie ; VAN NUFFEL, An M. T ; BONEHILL, Aude ; THIELEMANS, Kris ; NEYNS, Bart ; CORTHALS, Jurgen ; HEIRMAN, Carlo ; TUYAERTS, Sandra ; BENTEYN, Daphné ; DE CONINCK, Arlette ; VAN RIET, Ivan ; VERFAILLIE, Guy ; VANDELOO, Judith</creatorcontrib><description>The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC). This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containing autologous TriMix-DC co-electroporated with mRNA encoding a human leukocyte antigen class II-targeting signal linked to 1 of 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, and gp100) in patients with advanced melanoma. Thirty-five American Joint Committee on Cancer stage III/IV melanoma patients received autologous TriMix-DC (4 administrations 2 weeks apart). Immune monitoring was performed by evaluating skin biopsies of delayed type IV hypersensitivity (DTH) reactions for presence of vaccinal antigen-specific DTH-infiltrating lymphocytes (DIL). Thereafter, patients could receive interferon-alpha-2b (IFN-α-2b) 5 MU subcutaneously 3 times weekly and additional TriMix-DC every 8 weeks. TriMix-DC-related adverse events comprised grade 2 local injection site reactions (all patients), and grade 2 fever and lethargy (2 patients). Vaccinal antigen-specific DIL were found in 0/6 patients tested at vaccine initiation and in 12/21 (57.1%) assessed after the fourth vaccine. A positive postvaccination DTH test correlated with IL-12p70 secretion capacity of TriMix-DC. No objective responses to TriMix-DC alone were seen according to RECIST. Twenty-nine patients received IFN-α-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-α-2b combination therapy, 1 partial response and 5 stable disease (disease control of >6 months with regression of metastases) were observed in 17 patients with evaluable disease at baseline. In conclusion, this study demonstrated that therapeutic vaccination with autologous TriMix-DC is feasible, safe, and immunogenic and can be combined with sequential IFN-α-2b.</description><identifier>ISSN: 1524-9557</identifier><identifier>EISSN: 1537-4513</identifier><identifier>DOI: 10.1097/CJI.0b013e31821dcb31</identifier><identifier>PMID: 21577140</identifier><identifier>CODEN: JOIMF8</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adult ; Aged ; Antigens, Neoplasm - immunology ; Antineoplastic agents ; Biological and medical sciences ; Biopsy ; Cancer ; Cancer Vaccines - administration & dosage ; Cancer Vaccines - immunology ; CD27 Ligand - immunology ; CD27 Ligand - metabolism ; CD40 antigen ; CD40 Antigens - immunology ; CD40 Antigens - metabolism ; CD70 antigen ; Clinical trials ; Dendritic cells ; Dendritic Cells - cytology ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Dermatology ; Disease control ; Drug Therapy, Combination - methods ; Electroporation ; Female ; Fever ; Glycoprotein gp100 ; Histocompatibility antigen HLA ; Histocompatibility Antigens Class II - immunology ; Histocompatibility Antigens Class II - metabolism ; Humans ; Hypersensitivity (delayed) ; Hypersensitivity, Delayed - immunology ; Immunogenicity ; Immunostimulation ; Immunotherapy ; Interferon-alpha - administration & dosage ; Interleukin 12 ; Lymphocytes ; Male ; Medical sciences ; Melanoma ; Melanoma-associated antigen ; Metastases ; Middle Aged ; Monophenol monooxygenase ; mRNA ; Neoplasm Staging ; Pharmacology. Drug treatments ; Recombinant Proteins ; RNA, Messenger - immunology ; RNA, Messenger - metabolism ; Skin ; Skin Neoplasms - drug therapy ; Skin Neoplasms - immunology ; Skin Neoplasms - mortality ; Skin Neoplasms - pathology ; Survival Analysis ; TLR4 protein ; Toll-Like Receptor 4 - immunology ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors ; Tumors of the skin and soft tissue. Premalignant lesions ; Vaccination ; Vaccines</subject><ispartof>Journal of immunotherapy (1997), 2011-06, Vol.34 (5), p.448-456</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c368t-27d2523ad9e00aceca218fb40632f959e40c4a8f3f5613905646eab0c46033593</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24219616$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21577140$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WILGENHOF, Sofie</creatorcontrib><creatorcontrib>VAN NUFFEL, An M. T</creatorcontrib><creatorcontrib>BONEHILL, Aude</creatorcontrib><creatorcontrib>THIELEMANS, Kris</creatorcontrib><creatorcontrib>NEYNS, Bart</creatorcontrib><creatorcontrib>CORTHALS, Jurgen</creatorcontrib><creatorcontrib>HEIRMAN, Carlo</creatorcontrib><creatorcontrib>TUYAERTS, Sandra</creatorcontrib><creatorcontrib>BENTEYN, Daphné</creatorcontrib><creatorcontrib>DE CONINCK, Arlette</creatorcontrib><creatorcontrib>VAN RIET, Ivan</creatorcontrib><creatorcontrib>VERFAILLIE, Guy</creatorcontrib><creatorcontrib>VANDELOO, Judith</creatorcontrib><title>Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma</title><title>Journal of immunotherapy (1997)</title><addtitle>J Immunother</addtitle><description>The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC). This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containing autologous TriMix-DC co-electroporated with mRNA encoding a human leukocyte antigen class II-targeting signal linked to 1 of 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, and gp100) in patients with advanced melanoma. Thirty-five American Joint Committee on Cancer stage III/IV melanoma patients received autologous TriMix-DC (4 administrations 2 weeks apart). Immune monitoring was performed by evaluating skin biopsies of delayed type IV hypersensitivity (DTH) reactions for presence of vaccinal antigen-specific DTH-infiltrating lymphocytes (DIL). Thereafter, patients could receive interferon-alpha-2b (IFN-α-2b) 5 MU subcutaneously 3 times weekly and additional TriMix-DC every 8 weeks. TriMix-DC-related adverse events comprised grade 2 local injection site reactions (all patients), and grade 2 fever and lethargy (2 patients). Vaccinal antigen-specific DIL were found in 0/6 patients tested at vaccine initiation and in 12/21 (57.1%) assessed after the fourth vaccine. A positive postvaccination DTH test correlated with IL-12p70 secretion capacity of TriMix-DC. No objective responses to TriMix-DC alone were seen according to RECIST. Twenty-nine patients received IFN-α-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-α-2b combination therapy, 1 partial response and 5 stable disease (disease control of >6 months with regression of metastases) were observed in 17 patients with evaluable disease at baseline. In conclusion, this study demonstrated that therapeutic vaccination with autologous TriMix-DC is feasible, safe, and immunogenic and can be combined with sequential IFN-α-2b.</description><subject>Adult</subject><subject>Aged</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Cancer</subject><subject>Cancer Vaccines - administration & dosage</subject><subject>Cancer Vaccines - immunology</subject><subject>CD27 Ligand - immunology</subject><subject>CD27 Ligand - metabolism</subject><subject>CD40 antigen</subject><subject>CD40 Antigens - immunology</subject><subject>CD40 Antigens - metabolism</subject><subject>CD70 antigen</subject><subject>Clinical trials</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - cytology</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Dermatology</subject><subject>Disease control</subject><subject>Drug Therapy, Combination - methods</subject><subject>Electroporation</subject><subject>Female</subject><subject>Fever</subject><subject>Glycoprotein gp100</subject><subject>Histocompatibility antigen HLA</subject><subject>Histocompatibility Antigens Class II - immunology</subject><subject>Histocompatibility Antigens Class II - metabolism</subject><subject>Humans</subject><subject>Hypersensitivity (delayed)</subject><subject>Hypersensitivity, Delayed - immunology</subject><subject>Immunogenicity</subject><subject>Immunostimulation</subject><subject>Immunotherapy</subject><subject>Interferon-alpha - administration & dosage</subject><subject>Interleukin 12</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melanoma</subject><subject>Melanoma-associated antigen</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Monophenol monooxygenase</subject><subject>mRNA</subject><subject>Neoplasm Staging</subject><subject>Pharmacology. Drug treatments</subject><subject>Recombinant Proteins</subject><subject>RNA, Messenger - immunology</subject><subject>RNA, Messenger - metabolism</subject><subject>Skin</subject><subject>Skin Neoplasms - drug therapy</subject><subject>Skin Neoplasms - immunology</subject><subject>Skin Neoplasms - mortality</subject><subject>Skin Neoplasms - pathology</subject><subject>Survival Analysis</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 4 - immunology</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Toll-like receptors</subject><subject>Tumors of the skin and soft tissue. Premalignant lesions</subject><subject>Vaccination</subject><subject>Vaccines</subject><issn>1524-9557</issn><issn>1537-4513</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAUhS0EoqXwDxDyBrFK8TvxcjQUKCoPoQLL6Ma5oUaJPbUdBP8ej2YAiQ0rX1nfOfdxCHnM2Tlntn2-fXN5zgbGJUreCT66QfI75JRr2TZKc3l3XwvVWK3bE_Ig52-MCSOUuE9OBNdtyxU7JT-ubzDBDtfiHf0MzvkAxcdAv_hyQyHQzVriHL_GNdPl47sNvZjRlRR3MUHBkb7AMCa_F29xno8OSH2gH6oPhpIPTpvxOwRXBW9xhhAXeEjuTTBnfHR8z8inlxfX29fN1ftXl9vNVeOk6Uoj2lFoIWG0yBg4dCB4Nw2KGSkmqy0q5hR0k5y04dIybZRBGOqnYVJqK8_Is4PvLsXbFXPpF59dnRUC1qV6q5XRopP8v2RnOias7lQl1YF0KeaccOp3yS-Qfvac9ftw-hpO_284Vfbk2GAdFhz_iH6nUYGnRwCyg3lK9WQ-_-WU4NZwI38BkZiYrQ</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>WILGENHOF, Sofie</creator><creator>VAN NUFFEL, An M. T</creator><creator>BONEHILL, Aude</creator><creator>THIELEMANS, Kris</creator><creator>NEYNS, Bart</creator><creator>CORTHALS, Jurgen</creator><creator>HEIRMAN, Carlo</creator><creator>TUYAERTS, Sandra</creator><creator>BENTEYN, Daphné</creator><creator>DE CONINCK, Arlette</creator><creator>VAN RIET, Ivan</creator><creator>VERFAILLIE, Guy</creator><creator>VANDELOO, Judith</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope></search><sort><creationdate>20110601</creationdate><title>Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma</title><author>WILGENHOF, Sofie ; VAN NUFFEL, An M. T ; BONEHILL, Aude ; THIELEMANS, Kris ; NEYNS, Bart ; CORTHALS, Jurgen ; HEIRMAN, Carlo ; TUYAERTS, Sandra ; BENTEYN, Daphné ; DE CONINCK, Arlette ; VAN RIET, Ivan ; VERFAILLIE, Guy ; VANDELOO, Judith</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-27d2523ad9e00aceca218fb40632f959e40c4a8f3f5613905646eab0c46033593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Cancer</topic><topic>Cancer Vaccines - administration & dosage</topic><topic>Cancer Vaccines - immunology</topic><topic>CD27 Ligand - immunology</topic><topic>CD27 Ligand - metabolism</topic><topic>CD40 antigen</topic><topic>CD40 Antigens - immunology</topic><topic>CD40 Antigens - metabolism</topic><topic>CD70 antigen</topic><topic>Clinical trials</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - cytology</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Dermatology</topic><topic>Disease control</topic><topic>Drug Therapy, Combination - methods</topic><topic>Electroporation</topic><topic>Female</topic><topic>Fever</topic><topic>Glycoprotein gp100</topic><topic>Histocompatibility antigen HLA</topic><topic>Histocompatibility Antigens Class II - immunology</topic><topic>Histocompatibility Antigens Class II - metabolism</topic><topic>Humans</topic><topic>Hypersensitivity (delayed)</topic><topic>Hypersensitivity, Delayed - immunology</topic><topic>Immunogenicity</topic><topic>Immunostimulation</topic><topic>Immunotherapy</topic><topic>Interferon-alpha - administration & dosage</topic><topic>Interleukin 12</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Melanoma</topic><topic>Melanoma-associated antigen</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Monophenol monooxygenase</topic><topic>mRNA</topic><topic>Neoplasm Staging</topic><topic>Pharmacology. Drug treatments</topic><topic>Recombinant Proteins</topic><topic>RNA, Messenger - immunology</topic><topic>RNA, Messenger - metabolism</topic><topic>Skin</topic><topic>Skin Neoplasms - drug therapy</topic><topic>Skin Neoplasms - immunology</topic><topic>Skin Neoplasms - mortality</topic><topic>Skin Neoplasms - pathology</topic><topic>Survival Analysis</topic><topic>TLR4 protein</topic><topic>Toll-Like Receptor 4 - immunology</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Toll-like receptors</topic><topic>Tumors of the skin and soft tissue. Premalignant lesions</topic><topic>Vaccination</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WILGENHOF, Sofie</creatorcontrib><creatorcontrib>VAN NUFFEL, An M. 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T</au><au>BONEHILL, Aude</au><au>THIELEMANS, Kris</au><au>NEYNS, Bart</au><au>CORTHALS, Jurgen</au><au>HEIRMAN, Carlo</au><au>TUYAERTS, Sandra</au><au>BENTEYN, Daphné</au><au>DE CONINCK, Arlette</au><au>VAN RIET, Ivan</au><au>VERFAILLIE, Guy</au><au>VANDELOO, Judith</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma</atitle><jtitle>Journal of immunotherapy (1997)</jtitle><addtitle>J Immunother</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>34</volume><issue>5</issue><spage>448</spage><epage>456</epage><pages>448-456</pages><issn>1524-9557</issn><eissn>1537-4513</eissn><coden>JOIMF8</coden><abstract>The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC). This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containing autologous TriMix-DC co-electroporated with mRNA encoding a human leukocyte antigen class II-targeting signal linked to 1 of 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, and gp100) in patients with advanced melanoma. Thirty-five American Joint Committee on Cancer stage III/IV melanoma patients received autologous TriMix-DC (4 administrations 2 weeks apart). Immune monitoring was performed by evaluating skin biopsies of delayed type IV hypersensitivity (DTH) reactions for presence of vaccinal antigen-specific DTH-infiltrating lymphocytes (DIL). Thereafter, patients could receive interferon-alpha-2b (IFN-α-2b) 5 MU subcutaneously 3 times weekly and additional TriMix-DC every 8 weeks. TriMix-DC-related adverse events comprised grade 2 local injection site reactions (all patients), and grade 2 fever and lethargy (2 patients). Vaccinal antigen-specific DIL were found in 0/6 patients tested at vaccine initiation and in 12/21 (57.1%) assessed after the fourth vaccine. A positive postvaccination DTH test correlated with IL-12p70 secretion capacity of TriMix-DC. No objective responses to TriMix-DC alone were seen according to RECIST. Twenty-nine patients received IFN-α-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-α-2b combination therapy, 1 partial response and 5 stable disease (disease control of >6 months with regression of metastases) were observed in 17 patients with evaluable disease at baseline. In conclusion, this study demonstrated that therapeutic vaccination with autologous TriMix-DC is feasible, safe, and immunogenic and can be combined with sequential IFN-α-2b.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>21577140</pmid><doi>10.1097/CJI.0b013e31821dcb31</doi><tpages>9</tpages></addata></record> |
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| subjects | Adult Aged Antigens, Neoplasm - immunology Antineoplastic agents Biological and medical sciences Biopsy Cancer Cancer Vaccines - administration & dosage Cancer Vaccines - immunology CD27 Ligand - immunology CD27 Ligand - metabolism CD40 antigen CD40 Antigens - immunology CD40 Antigens - metabolism CD70 antigen Clinical trials Dendritic cells Dendritic Cells - cytology Dendritic Cells - immunology Dendritic Cells - metabolism Dermatology Disease control Drug Therapy, Combination - methods Electroporation Female Fever Glycoprotein gp100 Histocompatibility antigen HLA Histocompatibility Antigens Class II - immunology Histocompatibility Antigens Class II - metabolism Humans Hypersensitivity (delayed) Hypersensitivity, Delayed - immunology Immunogenicity Immunostimulation Immunotherapy Interferon-alpha - administration & dosage Interleukin 12 Lymphocytes Male Medical sciences Melanoma Melanoma-associated antigen Metastases Middle Aged Monophenol monooxygenase mRNA Neoplasm Staging Pharmacology. Drug treatments Recombinant Proteins RNA, Messenger - immunology RNA, Messenger - metabolism Skin Skin Neoplasms - drug therapy Skin Neoplasms - immunology Skin Neoplasms - mortality Skin Neoplasms - pathology Survival Analysis TLR4 protein Toll-Like Receptor 4 - immunology Toll-Like Receptor 4 - metabolism Toll-like receptors Tumors of the skin and soft tissue. Premalignant lesions Vaccination Vaccines |
| title | Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma |
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