title: Whole Cell Therapeutic Vaccine Modified With Hyper-IL6 for Combinational Treatment of Nonresected Advanced Melanoma.
abstract: Active specific immunotherapy of cancer requires an efficient induction and effector phase. The induction covers potent activation of anti-tumor response, whereas effector breaks the immunosuppression. We report efficacy of therapeutic melanoma vaccine (AGI-101H) used alone in advanced disease as a candidate for further combined treatment. In adjuvant setting in patients with resected metastases AGI-101H combined with surgery of recurring disease demonstrated long-term survival. Seventy-seven patients with nonresectable melanoma (8% IIIB, 21% IIIC, 71% IV) were enrolled. AGI-101H was administered 8× every 2 weeks, and then every month. At progression, maintenance was continued or induction was repeated and followed by maintenance. Median follow-up was 139.3 months. The median overall survival (OS) was 17.3 months; in patients with WHO 0-1 was 20.3 months. Complete response (CR) and partial response (PR) were observed in 19.4% and 9% of pts. Disease control rate was 54.5% of pts. The median CR+PR duration was 32 months. Reinduction was performed in 36.3% patients following disease progression with 46.6% of CR+PR. No grade 3/4 adverse events were observed. Treatment with AGI-101H of melanoma patients is safe and effective. AGI-101H is a good candidate for combinatorial treatment with immune check-points inhibitors or tumor hypoxia normalizators.
  
  
  BACKGROUND
  EudraCT Number 2008-003373-40.
authors.affiliation: From the Chair of Medical Biotechnology, University of Medical Sciences (JM, ML, MK, MW, MZ, AM); Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre (JM, A-KD, MW, AM); Department of Medical and Experimental Oncology, Clinical Hospital of Poznan University of Medical Sciences, Poznan, Poland (JM); Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, Belgium (TB); Biochemisches Institut, University Kiel, Kiel, Germany (SR-J); and BioContract Sp z o.o., Poznan, Poland (ML, MK, AM).
authors.forename: Jacek
authors.initials: J
authors.lastname: Mackiewicz
authors.forename: Aldona
authors.initials: A
authors.lastname: Karczewska-Dzionk
authors.forename: Maria
authors.initials: M
authors.lastname: Laciak
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kapcinska
authors.forename: Maciej
authors.initials: M
authors.lastname: Wiznerowicz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Burzykowski
authors.forename: Monika
authors.initials: M
authors.lastname: Zakowska
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mackiewicz
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D019947:Receptors, Interleukin-6 / Q000008:administration & dosage*; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D019496:Cancer Vaccines; D015850:Interleukin-6; D019947:Receptors, Interleukin-6