Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma

Sofie Wilgenhof; An Van Nuffel; Jurgen Corthals; Carlo Heirman; Sandra Tuyaerts; Daphné Benteyn; Arlette De Coninck; Ivan Van Riet; Guy Verfaillie; Judith Vandeloo; Aude Bonehill; Kris Thielemans; Bart Neyns

Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma

Sofie Wilgenhof, An Van Nuffel, Jurgen Corthals, Carlo Heirman, Sandra Tuyaerts, Daphné Benteyn, Arlette De Coninck, Ivan Van Riet, Guy Verfaillie, Judith Vandeloo, Aude Bonehill, Kris Thielemans, Bart Neyns

Research output: Contribution to journal › Article › peer-review

129 Citations (Scopus)

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-alpha-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-?-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-alpha-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-alpha-2b.

Original language	English
Pages (from-to)	448-456
Number of pages	9
Journal	Journal of Immunotherapy
Volume	34
Issue number	5
Publication status	Published - 2011

Keywords

dentric cell
interferon alpha-2b
triMix
immunotherapy
melanoma

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Wilgenhof, S., Van Nuffel, A., Corthals, J., Heirman, C., Tuyaerts, S., Benteyn, D., De Coninck, A., Van Riet, I., Verfaillie, G., Vandeloo, J., Bonehill, A., Thielemans, K., & Neyns, B. (2011). Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma. Journal of Immunotherapy, 34(5), 448-456. http://apps.isiknowledge.com.ezproxy.vub.ac.be:2048/full_record.do?product=UA&search_mode=GeneralSearch&qid=28&SID=R1@5Kol@FnpLohpK2Ak&page=1&doc=1&colname=WOS

Wilgenhof, Sofie ; Van Nuffel, An ; Corthals, Jurgen ; Heirman, Carlo ; Tuyaerts, Sandra ; Benteyn, Daphné ; De Coninck, Arlette ; Van Riet, Ivan ; Verfaillie, Guy ; Vandeloo, Judith ; Bonehill, Aude ; Thielemans, Kris ; Neyns, Bart. / Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma. In: Journal of Immunotherapy. 2011 ; Vol. 34, No. 5. pp. 448-456.

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title = "Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma",

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-alpha-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-?-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-alpha-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-alpha-2b.",

keywords = "dentric cell, interferon alpha-2b, triMix, immunotherapy, melanoma",

author = "Sofie Wilgenhof and {Van Nuffel}, An and Jurgen Corthals and Carlo Heirman and Sandra Tuyaerts and Daphn{\'e} Benteyn and {De Coninck}, Arlette and {Van Riet}, Ivan and Guy Verfaillie and Judith Vandeloo and Aude Bonehill and Kris Thielemans and Bart Neyns",

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Wilgenhof, S, Van Nuffel, A, Corthals, J, Heirman, C, Tuyaerts, S, Benteyn, D, De Coninck, A , Van Riet, I , Verfaillie, G, Vandeloo, J, Bonehill, A, Thielemans, K & Neyns, B 2011, 'Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma', Journal of Immunotherapy, vol. 34, no. 5, pp. 448-456. <http://apps.isiknowledge.com.ezproxy.vub.ac.be:2048/full_record.do?product=UA&search_mode=GeneralSearch&qid=28&SID=R1@5Kol@FnpLohpK2Ak&page=1&doc=1&colname=WOS>

Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma. / Wilgenhof, Sofie; Van Nuffel, An; Corthals, Jurgen; Heirman, Carlo; Tuyaerts, Sandra; Benteyn, Daphné; De Coninck, Arlette ; Van Riet, Ivan ; Verfaillie, Guy; Vandeloo, Judith; Bonehill, Aude; Thielemans, Kris ; Neyns, Bart.

In: Journal of Immunotherapy, Vol. 34, No. 5, 2011, p. 448-456.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma

AU - Wilgenhof, Sofie

AU - Van Nuffel, An

AU - Corthals, Jurgen

AU - Heirman, Carlo

AU - Tuyaerts, Sandra

AU - Benteyn, Daphné

AU - De Coninck, Arlette

AU - Van Riet, Ivan

AU - Verfaillie, Guy

AU - Vandeloo, Judith

AU - Bonehill, Aude

AU - Thielemans, Kris

AU - Neyns, Bart

PY - 2011

Y1 - 2011

N2 - 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-alpha-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-?-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-alpha-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-alpha-2b.

AB - 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-alpha-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-?-2b after the fourth vaccine without unexpected adverse events. During TriMix-DC/IFN-alpha-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-alpha-2b.

KW - dentric cell

KW - interferon alpha-2b

KW - triMix

KW - immunotherapy

KW - melanoma

M3 - Article

VL - 34

SP - 448

EP - 456

JO - Journal of Immunotherapy

JF - Journal of Immunotherapy

SN - 1524-9557

IS - 5

ER -

Therapeutic Vaccination With an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Advanced Melanoma

Abstract

Keywords

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