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Incomplete Freund’s adjuvant reduces arginase and enhances Th1 dominance, TLR signaling and CD40 ligand expression in the vaccine site microenvironment
- Source :
- Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020)
- Publication Year :
- 2020
- Publisher :
- BMJ Publishing Group, 2020.
-
Abstract
- Background Immunogenicity of cancer vaccines is impacted by adjuvants and schedule, but systematic assessments of their effects have not been performed. Montanide ISA-51, an incomplete Freund’s adjuvant (IFA), is used in many vaccine trials, but concerns have been raised about negative effects in murine studies. We found in humans that IFA enhances systemic immune responses and that repeat vaccination at one site (same site vaccination (SSV)) creates tertiary lymphoid structures (TLS) in the vaccine site microenvironment (VSME). We hypothesized that vaccination with peptides+IFA+pICLC or SSV×3 with peptides in IFA would create an immunogenic milieu locally at the VSME, with activated dendritic cells (DC), TLS-associated chemokines and a Th1-dominant VSME.Methods Biopsies of the VSME were obtained from participants on two clinical trials who were immunized with multiple melanoma peptides (MELITAC 12.1) in adjuvants comprising IFA and/or the TLR3-agonist pICLC. Biopsies were obtained either a week after one vaccine or a week after SSV×3. Controls included normal skin and skin injected with IFA without peptides. Gene expression analysis was performed by RNAseq.Results VSME samples were evaluated from 27 patients. One vaccine with peptides in pICLC+IFA enhanced expression of CD80, CD83, CD86 (p
- Subjects :
- Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Subjects
Details
- Language :
- English
- ISSN :
- 20200005 and 20511426
- Volume :
- 8
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Journal for ImmunoTherapy of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.23619684f92f4a40b5f5f46f722ea09b
- Document Type :
- article
- Full Text :
- https://doi.org/10.1136/jitc-2020-000544