PMID- 32013270 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230106 IS - 2076-393X (Print) IS - 2076-393X (Electronic) IS - 2076-393X (Linking) VI - 8 IP - 1 DP - 2020 Jan 29 TI - Immune Therapy Targeting E6/E7 Oncogenes of Human Paillomavirus Type 6 (HPV-6) Reduces or Eliminates the Need for Surgical Intervention in the Treatment of HPV-6 Associated Recurrent Respiratory Papillomatosis. LID - 10.3390/vaccines8010056 [doi] LID - 56 AB - : Background: Recurrent respiratory papillomatosis (RRP) is a rare disorder characterized by the generation of papillomas of the aerodigestive tract, usually associated with human papilloma virus (HPV) subtypes 6, 11. INO-3106 is a DNA plasmid-based immunotherapy targeting E6 and E7 proteins of HPV6, in order to create a robust immune T cell response. METHODS: Testing of INO-3016 in animal models confirmed immunogenicity of the DNA-based therapy. A single-site open-label Phase 1 study was initiated for patients with HPV6-positive RRP. Patients were dosed with INO-3106 with or without INO-9012, a DNA plasmid immunotherapy that encodes IL-12, delivered intramuscularly (IM) in combination with electroporation (EP) with the CELLECTRA((R)) device. Patients received an escalating dose of INO-3106, 3 mg once and then 6 mg for three additional doses, each dose three weeks apart, with the third and fourth doses co-administered with INO-9012. The primary objective of the study was to evaluate the safety and tolerability of INO-3106 with and without INO-9012. The secondary objective was to determine cellular immune responses to INO-3106 with and without INO-9012. Exploratory objectives included preliminary clinical efficacy to the therapy. RESULTS: Three patients were enrolled in this study, of which two had RRP. Study therapy was well-tolerated, with no related serious adverse events and all related adverse events (AEs) were low-grade. Injection site pain was the most common related AE reported. Immunogenicity was evidenced by multiple immune assays showing engagement and expansion of an HPV6-specific cellular response, including cytotoxic T cells. Preliminary efficacy was demonstrated in patients with RRP in the form of reduction in need for surgical intervention for papilloma growth. Prior to intervention, both patients required surgical intervention approximately every 180 days. One patient demonstrated a greater than three-fold increase in surgery avoidance (584 days) and the other patient remains completely surgery-free as of the last contact at 915 days, a greater than 5-fold increase in surgery interval. CONCLUSION: INO-3106 with and without INO-9012 was well tolerated, immunogenic and demonstrated preliminary efficacy in patients with HPV6-associated RRP aerodigestive lesions. Further clinical study is indicated. FAU - Aggarwal, Charu AU - Aggarwal C AD - Division of Hematology Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA. FAU - Cohen, Roger B AU - Cohen RB AD - Division of Hematology Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA. FAU - Morrow, Matthew P AU - Morrow MP AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Kraynyak, Kimberly A AU - Kraynyak KA AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Sylvester, Albert J AU - Sylvester AJ AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Cheung, Jocelyn AU - Cheung J AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Dickerson, Kelsie AU - Dickerson K AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Schulten, Veronique AU - Schulten V AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Knoblock, Dawson AU - Knoblock D AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Gillespie, Elisabeth AU - Gillespie E AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Bauml, Joshua M AU - Bauml JM AD - Division of Hematology Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA. FAU - Yan, Jian AU - Yan J AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Diehl, Malissa AU - Diehl M AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Boyer, Jean AU - Boyer J AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Dallas, Michael AU - Dallas M AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Kim, J Joseph AU - Kim JJ AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. FAU - Weiner, David B AU - Weiner DB AD - The Wistar Institute Vaccine and Immunotherapy Center, Philadelphia, PA 19104, USA. FAU - Skolnik, Jeffrey M AU - Skolnik JM AD - Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA 19462, USA. LA - eng GR - P30 CA010815/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20200129 PL - Switzerland TA - Vaccines (Basel) JT - Vaccines JID - 101629355 PMC - PMC7158680 OTO - NOTNLM OT - HPV OT - RRP OT - immunotherapy COIS- Authors employed by Inovio Pharmaceuticals are supported financially by that entity. Non-Inovio authors have no conflicts to disclose. EDAT- 2020/02/06 06:00 MHDA- 2020/02/06 06:01 PMCR- 2020/01/29 CRDT- 2020/02/05 06:00 PHST- 2019/10/28 00:00 [received] PHST- 2019/11/15 00:00 [revised] PHST- 2020/01/23 00:00 [accepted] PHST- 2020/02/05 06:00 [entrez] PHST- 2020/02/06 06:00 [pubmed] PHST- 2020/02/06 06:01 [medline] PHST- 2020/01/29 00:00 [pmc-release] AID - vaccines8010056 [pii] AID - vaccines-08-00056 [pii] AID - 10.3390/vaccines8010056 [doi] PST - epublish SO - Vaccines (Basel). 2020 Jan 29;8(1):56. doi: 10.3390/vaccines8010056.