Immune Therapy Targeting E6/E7 Oncogenes of Human Papillomavirus Type 6 (HPV-6) Reduces or Eliminates the Need for Surgical Intervention in the Treatment of HPV-6 Associated Recurrent Respiratory Papillomatosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Antigenic 3D Modeling
2.2. Immunization of Mice
2.3. IFN-γ ELISpot Assay
2.4. CD8+ T-Cell Depletion of Mouse Samples
3. Clinical Study
3.1. Clinical Study Population
3.2. Immunotherapy and Electroporation Using CELLECTRA® Device
3.3. Study Design
3.4. Safety Assessments
3.5. HPV6 Specific ELISA
3.6. HPV6 Specific Flow Cytometry
3.7. HPV6 Specific PBMC Stimulation for Gene Expression Analysis
3.8. Multiplexed Gene Expression Analysis
3.9. Statistical Methods
4. Results
4.1. INO-3106 Displays Immunogenicity in Animal Models
4.2. INO-3106 Is Tolerable, Immunogenic and Potentially Effective in Patients with RRP
4.2.1. Patient Characteristics and Disposition
4.2.2. Safety and Tolerability of INO-3106 and INO-9012 with Electroporation (EP)
4.3. INO-3106 Induces Humoral Immune Reactivity in Patients with RRP
4.4. INO-3106 Induces the Expression of Activation Markers and Lytic Proteins in T Cells from Treated Patients with RRP
4.5. INO-3106 Changes Immune Transcriptional Profiles of T Cells in RRP Patients
4.6. INO-3106 Reduces the Need for Surgical Intervention for the Treatment of RRP
5. Discussion
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Markers Co-Expressed on CD8+ T Cells: | Before INO-3106 (%) | After INO-3106 (%) |
---|---|---|
CD38+Ki67+ | 0.49 | 3.95 |
Ki67+ | 0.45 | 3.88 |
CD38+Ki67+Prf+ | 0.53 | 3.93 |
CD38+Ki67+GrzA+Prf+ | 0.58 | 3.95 |
Ki67+GrzA+Prf+ | 0.53 | 3.91 |
Ki67+Prf+ | 0.48 | 3.84 |
Ki67+GrzB+Prf+ | 0.50 | 3.66 |
CD38+Ki67+GrzA+GrzB+Prf+ | 0.51 | 3.66 |
CD38+Ki67+GrzB+Prf+ | 0.51 | 3.66 |
Ki67+GrzA+GrzB+Prf+ | 0.51 | 3.66 |
Markers Co-Expressed on CD8+ T Cells: | Before INO-3106 (%) | After INO-3106 (%) |
---|---|---|
CD38+CD137+Ki67+GrzB+Prf+ | 0.35 | 0.51 |
CD38+CD69+CD137+ Ki67+GrzB+Prf+ | 0.35 | 0.48 |
CD137+Ki67+GrzB+Prf+ | 0.36 | 0.48 |
CD38+CD137+Ki67+ GrzA+GrzB+Prf+ | 0.36 | 0.48 |
CD69+CD137+Ki67+GrzB+Prf+ | 0.36 | 0.47 |
CD38+CD69+CD137+Ki67+ GrzA+GrzB+Prf+ | 0.36 | 0.46 |
CD137+Ki67+GrzA+GrzB+Prf+ | 0.37 | 0.46 |
CD38+CD137+GrzB+Prf+ | 0.41 | 0.49 |
CD38+Ki67+Gnly+GrzA+Prf+ | 0.00 | 0.08 |
CD38+Gnly+ | 0.00 | 0.08 |
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Aggarwal, C.; Cohen, R.B.; Morrow, M.P.; Kraynyak, K.A.; Sylvester, A.J.; Cheung, J.; Dickerson, K.; Schulten, V.; Knoblock, D.; Gillespie, E.; et al. Immune Therapy Targeting E6/E7 Oncogenes of Human Papillomavirus Type 6 (HPV-6) Reduces or Eliminates the Need for Surgical Intervention in the Treatment of HPV-6 Associated Recurrent Respiratory Papillomatosis. Vaccines 2020, 8, 56. https://doi.org/10.3390/vaccines8010056
Aggarwal C, Cohen RB, Morrow MP, Kraynyak KA, Sylvester AJ, Cheung J, Dickerson K, Schulten V, Knoblock D, Gillespie E, et al. Immune Therapy Targeting E6/E7 Oncogenes of Human Papillomavirus Type 6 (HPV-6) Reduces or Eliminates the Need for Surgical Intervention in the Treatment of HPV-6 Associated Recurrent Respiratory Papillomatosis. Vaccines. 2020; 8(1):56. https://doi.org/10.3390/vaccines8010056
Chicago/Turabian StyleAggarwal, Charu, Roger B. Cohen, Matthew P. Morrow, Kimberly A. Kraynyak, Albert J. Sylvester, Jocelyn Cheung, Kelsie Dickerson, Veronique Schulten, Dawson Knoblock, Elisabeth Gillespie, and et al. 2020. "Immune Therapy Targeting E6/E7 Oncogenes of Human Papillomavirus Type 6 (HPV-6) Reduces or Eliminates the Need for Surgical Intervention in the Treatment of HPV-6 Associated Recurrent Respiratory Papillomatosis" Vaccines 8, no. 1: 56. https://doi.org/10.3390/vaccines8010056