A publication in the Journal for ImmunoTherapy of Cancer in October 2022 by researchers at the Leiden University Medical Centre (LUMC) investigated the safety and immunogencity of ISA Pharmaceuticals’ Amplivant adjuvant and Synthetic Long Peptide (SLP) therapeutic vaccine technology. ISA stated in November 2022 that it is “delighted” with the publication, which demonstrates a “favourable safety profile”. The study was expanded from initial approval to enrol oropharyngeal squamous cell carcinoma (OPSCC) patients after “treatment with curative intent” to include patients with “an HPV16 positive (pre-)malignant lesion following standard treatment”.
The study in context
The authors of the publication note that “cancer vaccines are a promising strategy for cancer immunotherapy”. Furthermore, SLP based cancer vaccines are “safe, able to induce functional tumour-specific T cells, and show clinical efficacy”. However, they require combination treatments because they have “no intrinsic adjuvant”. Preclinical studies had revealed that “chemically well-defined adjuvants” such as Toll-like receptor (TLR) ligands can improve synthetic peptide cancer vaccines.
ISA’s Amplivant is one such ligand, which is “chemically adapted to optimally interact with the binding domain of the TLR2/TL1 heterodimer receptor to induce improved immunological activity”.
“Molecularly defined, self-adjuvanting peptide vaccines have the potency to cause local innate immune activation, antigen-targeting to dendritic cells (DCs) and DC activation, together leading to efficient T cell activation.”
In order to explore to potency of Amplivant-conjugated SLP vaccines the researchers used SLP derived from the human papilloma virus type 16 (HPV16) E6 oncoprotein amino acid (aa) sequence. Previous studies have demonstrated that spontaneous HPV16-specific T cell responses “occur but are weak” and unable to control tumour outgrowth.
The study is the first in human Phase I trial to establish safety and immunogenicity of Amplivant conjugated to HPV16 E6-SLP. Administered intradermally to take advantage of the “direct loading potency of skin-resident DCs”, the vaccine was injected 3 times in 4 dose cohorts. Between 2015 and 2020, 25 patients were enrolled.
“Patients were eligible for inclusion if they were at least 18 years of age, had previously documented evidence of an HPV16 positive (pre-)malignant lesion following standard curative treatment and were without residual disease based on physical examination between 4 and 16 weeks after therapy.”
Further inclusion criteria were applied. The vaccine comprised two HPV 16 E6 SLOP sequences, and the Amplivant-conjugated SLPs were manufactured and tested in The Netherlands. The trial included 2 weeks of screening, 6 weeks of vaccination treatment, and follow-up visits throughout the 20 weeks after the final dose of the vaccine.
Conclusions and limitations
The authors state that the study shows the vaccine to be “safe with only minimal and mostly local side effects”. In this study, CD4+ T cell responses were “more frequently found compared with CD8+ T cell responses”. This is “consistent” with previous results.
The authors note that “trial set up and patient availability” caused an “unfortunately unbalanced” male-female ratio. Despite this, they believe that the “unintentionally skewed” ratio didn’t influence response outcomes.
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