PEPTIDE VACCINE FORMULATION CONTROLS THE DURATION OF ANTIGEN PRESENTATION AND MAGNITUDE OF TUMOR‐SPECIFIC CD8+ T CELL RESPONSE

Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that the duration of antigen presentation critically affected the quantity and quality of T cell response and subsequent anti‐tumor efficacy. Here we describe L‐tyrosine amino acid‐based microparticles as a novel peptide vaccine adjuvant for the induction of tumor‐specific T cells. L‐tyrosine microparticles did not induce inflammasome activation, but instead extended antigen presentation time. The consequent prolongation in antigen presentation translated into prolonged T cell proliferation and superior numbers and anti‐tumor function of vaccination‐induced CD8+ T cells. Indeed, prolonging antigen presentation by repeated injection of peptide in saline resulted in an increase in T cell numbers similar to that observed after vaccination with peptide/L‐tyrosine microparticles. These results suggest that the duration of antigen presentation is critical for optimal induction of anti‐tumor T cells, and can be manipulated through proper vaccine formulation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The use of participatory approaches to evaluate the socio-economic factors impairing the efficacy of animal health surveillance systems

The need to set up efficient and sustainable surveillance networks is a major concern which must be continually placed at the heart of the overall issue of development. In developing countries, the political priority to reduce poverty means that it is vital to include social aspects in public decision making on health management in general. This focus on social aspects can be considered all the more important regarding surveillance as it is deeply embedded in agents’ everyday life. The flow of information about animal health involves different non-monetary costs, ensuing from stigmatization or from social pressure to withhold or disclose information. Understanding, measuring and alleviating these social costs of information is required to ensure the effectiveness and viability of surveillance. The present study considers the case of highly pathogenic avian influenza surveillance in Vietnam. It aims at establishing a protocol allowing for understanding and quantifying social costs incurred by surveillance agents at the community level. In this prospect, tools and concepts from anthropology, participative epidemiology and experimental economics were combined. More particularly, social network analysis, participatory observation, companion modeling and stated preference surveys were applied for the thorough examination of constraints and costs of health information flows. The opportunity for the scaling-up of such methodologies and for the inclusion of the so-elicited quantitative values in socio-economic evaluation of surveillance systems are discussed

Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction.

T cells become dysfunctional when they encounter self antigens or are exposed to chronic infection or to the tumour microenvironmen