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

• DOI: 10.1097/cji.0b013e31821dcb31
• Publication Date: 2011-05-14T11:08:19Z
• Authors: Sofie Wilgenhof; An M.T. 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
• Keywords: electroporation; Adult; Male; 0301 basic medicine; Interferon-alpha/administration & dosage; Drug Therapy, Combination/methods; Dendritic Cells/cytology; Interferon alpha-2; Cancer Vaccines; 03 medical and health sciences; Histocompatibility Antigens Class II/immunology; Antigens, Neoplasm; Skin Neoplasms/drug therapy; melanoma; Humans; Hypersensitivity, Delayed; RNA, Messenger; CD40 Antigens/immunology; CD40 Antigens; Melanoma; dentric cell; Antigens, Neoplasm/immunology; Aged; Neoplasm Staging; Cancer Vaccines/administration & dosage; Toll-Like Receptor 4/immunology; Histocompatibility Antigens Class II; Interferon-alpha; Dendritic Cells; Middle Aged; vaccination; Survival Analysis; Recombinant Proteins; 3. Good health; RNA, Messenger/immunology; Electroporation; interferon alpha-2b; CD27 Ligand/immunology; Drug Therapy, Combination; Female; immunotherapy; Hypersensitivity, Delayed/immunology; TriMix; CD27 Ligand

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, immunogenicity a therapeutic vaccination containing autologous TriMix-DC co-electroporated human leukocyte antigen class II-targeting signal linked to 1 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, gp100) in patients advanced melanoma. Thirty-five American Joint Committee on Cancer stage III/IV melanoma received (4 administrations 2 weeks apart). Immune monitoring was performed evaluating skin biopsies delayed type IV hypersensitivity (DTH) reactions for presence vaccinal antigen-specific DTH-infiltrating lymphocytes (DIL). Thereafter, could receive interferon-alpha-2b (IFN-α-2b) 5 MU subcutaneously 3 times weekly additional every 8 weeks. TriMix-DC-related adverse events comprised grade local injection site (all patients), fever lethargy (2 patients). Vaccinal DIL were found 0/6 tested at vaccine initiation 12/21 (57.1%) assessed after fourth vaccine. A positive postvaccination DTH test correlated IL-12p70 secretion TriMix-DC. No objective responses alone seen according RECIST. Twenty-nine IFN-α-2b without unexpected events. During TriMix-DC/IFN-α-2b combination therapy, partial response stable disease (disease control >6 months regression metastases) observed 17 evaluable baseline. In conclusion, this study demonstrated that feasible, safe, immunogenic can be combined sequential IFN-α-2b.