RESUMEN
Recent breakthroughs in cancer immunotherapy have provided unprecedented clinical benefits to human cancer patients. Cancer is also one of the most common causes of death in pet dogs. Thus, canine-specific immune therapies targeting similar signaling pathways can provide better treatment options for canine cancer patients. Here, we describe the development and characterization of two canine-specific anti-OX40 agonists to activate OX40 signaling. We show that canine OX40, like human OX40, is not expressed on resting T cells, and its expression is markedly increased on canine CD4 T cells and Tregs after stimulation with concanavalin A (Con-A). cOX40 is also expressed on tumor-infiltrating lymphocytes (TILs) in canine osteosarcoma patients. The canine-specific OX40 agonists strongly activates cPBMCs by increasing IFN-γ expression and do not require Fc receptor-mediated cross-linking for OX40 agonism. Together, these results suggest that cFcOX40L proteins are potent OX40 agonists and have the potential to enhance antitumor immunity in canine cancer patients.
RESUMEN
PURPOSE: Individuals with substance use disorders (SUD) are at an elevated risk for suicide. Abstinence and drug-related treatment outcomes remain integral to SUD treatment, but recovery incorporates more than just the absence of substance use or mental illness and including positive mental health indices in assessment and treatment of suicidality is needed. AIMS: The current study investigates the role of traditional indicators of recovery, as well as positive psychology constructs, in predicting suicidal ideation following residential SUD treatment. METHOD: The study utilized a longitudinal design with baseline and 3-month postdischarge follow-up assessments of 791 individuals who attended residential SUD treatment in Australia. RESULTS: Rates of suicidal ideation decreased from baseline to follow-up, and the magnitude of change in most indices was associated with suicidal ideation at follow-up assessment. In a hierarchical logistic regression, baseline suicidal ideation, as well as a reduction in psychological distress, increase in refusal self-efficacy, and increase in self-forgiveness, emerged as significant predictors of follow-up suicidal ideation. The final model correctly classified 98.8% of participants as not experiencing SI, and 8.7% of participants as experiencing SI at follow-up, resulting in a total predictive accuracy of 86.9%. CONCLUSIONS: The results suggested that changes in traditional recovery indices may facilitate reductions in suicidality. As a whole, changes in positive psychology indices did not add to the ability to predict suicidal ideation once traditional indices had been accounted for, but this does not preclude the importance of these indices to SUD treatment and suicide prevention efforts.