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

Barriers to Utilization of Prescription Drug Monitoring Programs Among Prescribing Physicians and Advanced Practice Registered Nurses at Veterans Health Administration Facilities in Oregon

Objective To identify barriers to using state prescription drug monitoring programs (PDMPs) among prescribing physicians and advanced practice registered nurses across a variety of Veterans Health Administration (VA) settings in Oregon. Design In-person and telephone-based qualitative interviews and user experience assessments conducted with 25 VA prescribers in 2018 probed barriers to use of state PDMPs. Setting VA health care facilities in Oregon. Subjects Physicians (N = 11) and advanced practice registered nurses (N = 14) who prescribed scheduled medications, provided care to patients receiving opioids, and used PDMPs in their clinical practice. Prescribers were stationed at VA medical centers (N = 10) and community-based outpatient clinics (N = 15); medical specialties included primary care (N = 10), mental health (N = 9), and emergency medicine (N = 6). Methods User experience was analyzed using descriptive statistics. Qualitative interviews were analyzed using conventional content analysis methodology. Results The majority of physicians (64%) and advanced practice registered nurses (79%) rated PDMPs as “useful.” However, participants identified both organizational and software design issues as barriers to their efficient use of PDMPs. Organizational barriers included time constraints, clinical team members without access, and lack of clarity regarding the priority of querying PDMPs relative to other pressing clinical tasks. Design barriers included difficulties entering or remembering passwords, unreadable data formats, time-consuming program navigation, and inability to access patient information across state lines. Conclusions Physicians and advanced practice registered nurses across diverse VA settings reported that PDMPs are an important tool and contribute to patient safety. However, issues regarding organizational processes and software design impede optimal use of these resources