Although the epitopic breadth of HIV-1-specific CD8 T lymphocyte (CTL) responses has been described, the T cell receptor (TCR) diversity of virus-specific cells remains poorly defined.To address this issue, we applied a novel technique for subtractive analysis of the HIV-1-specific CTL repertoire, combining specific deletion of peptide-specific cells by 5-fluorouracil with TCR spectratyping to identify clonal breadth of CTL recognizing individual peptides.Comprehensive analysis of an infected individual reveals that nine identified HIV-1-specific responses are comprised of at least 38 distinct T-cell clones (ranging from two to 10 distinct clones per epitope).Given the potentially crucial role of T-cell receptor breadth for viral recognition and avoidance of escape, this subepitopic analysis of CTL may offer an important measure of cellular immunity for pathogenesis and vaccine studies.
Meeting abstracts The TLR 7/8 agonist, Resiquimod has been shown to induce local activation of immune cells, production of cytokines, and antigen-presentation by dendritic cells, features desirable for cancer vaccine adjuvants. In this study, we evaluated the safety and immunogenicity of
<p>Supplemental Figure 3. Selected BTM geneset enrichments (FDR < 0,25) of SD (patient 002) and PD patients (004 and 008) at tumor site. Gene names of enriched genesets are publicly available online in supplemental data for original paper23.</p>
<p>Supplemental Figure 4. Selected Broad Institute C7 immune geneset enrichments (FDR < 0,25). Gene names of enriched genesets are publicly available online at MSigDB: http://software.broadinstitute.org/gsea/msigdb/index.jsp.</p>
TPS3114 Background: Mutation-derived tumor antigens (MTAs) arise as a direct result of somatic variations, including nucleotide substitutions, insertions, and deletions that occur during carcinogenesis. These somatic variations can be characterized via genetic sequencing and used to identify MTAs. We propose a platform for a fully-personalized MTA-based vaccine in the adjuvant treatment of solid tumors. Methods: This clinical trial is a single-arm, open label, proof-of-concept phase I study designed to test the safety and immunogenicity of the Personalized Genomic Vaccine 001 (PGV001). The single-center study will enroll 20 eligible subjects with histological diagnosis of the following tumor types: (a) head and neck squamous cell cancer, (b) non-small cell lung cancer, (c) ductal or lobular breast cancer, (d) serous carcinoma of the ovary, uterine adnexa, (e) urothelial carcinoma of renal pelvis or bladder, (f) cutaneous squamous cell cancer. Subjects must have no measurable disease at time of first vaccine administration, and 5-year disease recurrence risk of > 30%. Patients will receive 10 doses of PGV001 as well as 10 doses of poly-ICLC (toll-like receptor-3 agonist, vaccine adjuvant), administered 1 day after PGV001 vaccination. Toxicity (endpoint 1) will be defined by Common Terminology Criteria for Adverse Events v5.0. Blood samples will be collected at various time points for immune response monitoring of MTA-specific humoral and cellular immune responses. For each patient, immunogenicity (endpoint 2) will be defined as an epitope-specific T cell response, detectable in peripheral blood samples after PGV001 vaccination. The change in the frequency of vaccine-induced epitope-specific T lymphocyte populations post-vaccination relative to baseline will be determined using mixed effects linear regression modeling. Conclusions: Our clinical trial will test for the first time the safety and immunogenicity of PGV001 in patients with multiple solid cancers. The information learned from this clinical trial will instruct the next generation of MTA-based vaccines, future development of immunotherapeutic approaches and rational combinations. Clinical trial information: NCT02721043.
### O1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cells #### Andreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1,
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