First-in-human study investigating the safety and immunogenicity of ISA’s proprietary Amplivant adjuvant conjugated to human papillomavirus type 16 (HPV16) Synthetic Long Peptides (SLPs).
SLPs conjugated to Amplivant elicit a significant, strong immune response and dose related systemic T cell immunity when injected intradermally.
Study demonstrates that SLPs conjugated to Amplivant have highly favourable tolerability and safety when used as an intradermal therapeutic vaccine.
Oegstgeest, The Netherlands, 08 November 2022 – ISA is delighted to announce publication by Leiden University Medical Center (LUMC) of a phase 1 clinical study using ISA’s proprietary Amplivant® adjuvant and Synthetic Long Peptide (SLP®) therapeutic vaccine technology. The study was recently published in the Journal for ImmunoTherapy of Cancer. This open access paper is entitled ‘Intradermal vaccination of HPV-16 E6 synthetic peptides conjugated to an optimized Toll-like receptor 2 ligand shows safety and potent T cell immunogenicity in patients with HPV16 positive (pre-)malignant lesions’. The study can be found at: https://doi.org/10.1136/jitc-2022-005016.
Amplivant is a molecularly optimized Toll-like receptor 1/2 ligand that can be covalently conjugated to tumour peptide antigens. In preclinical models Amplivant-adjuvanted SLPs strongly enhance antigen presentation by dendritic cells, T cell priming, and induce effective antitumor responses.
This first-in-human clinical study demonstrated a favourable safety profile without serious adverse events and a strong immune response generated with only two Amplivant-conjugated HPV16 SLPs. The study concludes that Amplivant-conjugated SLPs can be safely used as an intradermal therapeutic vaccine to induce HPV16-specific T cell immunity in previously treated patients with HPV16-positive (pre-)malignancies. Vaccine dose escalation in 25 patients caused a corresponding increase in systemic T cell immunity.
Amplivant was conjugated to two SLPs derived from the two most immunodominant regions of the HPV16 E6 oncoprotein. Patients received 3 doses intradermally, three times a week, and with a 3-week interval in four dose groups (1, 5, 20 or 50 µg per conjugated peptide). Peptide-specific T cell immune responses were determined in PBMC’s from blood samples taken before, during and after vaccination.