title: Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma.
abstract: OBJECTIVE
  Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic mRNA (TriMixDC-MEL) are immunogenic and have antitumor activity as a monotherapy in patients with pretreated advanced melanoma. Ipilimumab, an immunoglobulin G1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated protein 4 receptor that counteracts physiologic suppression of T-cell function, improves the overall survival of patients with advanced melanoma. This phase II study investigated the combination of TriMixDC-MEL and ipilimumab in patients with pretreated advanced melanoma.
  
  
  METHODS
  Thirty-nine patients were treated with TriMixDC-MEL (4 × 10(6) cells administered intradermally and 20 × 10(6) cells administered intravenously) plus ipilimumab (10 mg/kg every 3 weeks for a total of four administrations, followed by maintenance therapy every 12 weeks in patients who remained progression free). Six-month disease control rate according to the immune-related response criteria served as the primary end point.
  
  
  RESULTS
  The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post-DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients. There was no grade 5 adverse event.
  
  
  CONCLUSIONS
  The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging rate of highly durable tumor responses in patients with pretreated advanced melanoma.
authors.affiliation: Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Sofie
authors.initials: S
authors.lastname: Wilgenhof
authors.affiliation: Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Corthals
authors.affiliation: Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Carlo
authors.initials: C
authors.lastname: Heirman
authors.affiliation: Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Nicolas
authors.initials: N
authors.lastname: van Baren
authors.affiliation: Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lucas
authors.affiliation: Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Pia
authors.initials: P
authors.lastname: Kvistborg
authors.affiliation: Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.affiliation: Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands. Bart.Neyns@uzbrussel.be.
authors.forename: Bart
authors.initials: B
authors.lastname: Neyns
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002478:Cells, Cultured; D017024:Chemotherapy, Adjuvant; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D018274:Electroporation; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D012333:RNA, Messenger