In vivo CAR T-cell generation in nonhuman primates using lentiviral vectors displaying a multidomain fusion ligand.

ABSTRACT: Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformative efficacy in treating B-cell malignancies. However, high costs and manufacturing complexities hinder their widespread use. To overcome these hurdles, we have developed the VivoVec platform, a lentiviral vector capable of generating CAR T cells in vivo. Here, we describe the incorporation of T-cell activation and costimulatory signals onto the surface of VivoVec particles (VVPs) in the form of a multidomain fusion protein and show enhanced in vivo transduction and improved CAR T-cell antitumor functionality. Furthermore, in the absence of lymphodepleting chemotherapy, administration of VVPs into nonhuman primates resulted in the robust generation of anti-CD20 CAR T cells and the complete depletion of B cells for >10 weeks. These data validate the VivoVec platform in a translationally relevant model and support its transition into human clinical testing, offering a paradigm shift in the field of CAR T-cell therapies.

Reconnecting Homeless Adolescents and Their Families: Correlates of Participation in a Family Intervention.

Behavioral family interventions are an effective way to intervene to prevent negative developmental outcomes for adolescents. Participation in family interventions encompasses behavioral and cognitive/attitudinal dimensions, among others, indicated by retention and engagement, respectively. Two dimensions of participation, retention and engagement, in a family intervention were examined in a sample of newly homeless adolescents and their parents or guardians. Correlates of participation included parents with more income and less perceived family conflict and adolescents with higher endorsement of depression, anxiety, somatization, obsessive-compulsive, phobic, and psychotic symptoms on the Brief Symptom Inventory (BSI). Stronger therapeutic alliance was correlated with being more distressed (i.e., lower income, more hostility), being a female adolescent participant, and having greater comfort discussing sex with parents. Furthermore, parents and adolescents with greater distress and thus greater need were more apt to finish the intervention. The finding that families who were experiencing more distress had higher alliance scores suggests that there is an additional need for development of interventions for families in crisis. Both participant and provider perceptions are also important in development of a strong therapeutic alliance. This study's findings have implications for further exploration of the development of cultural humility and improving mental health literacy among facilitators of behavioral interventions.

Understanding, unpacking, and eliminating health disparities: A prescription for health equity promotion through behavioral and psychological research-An introduction.

Research on health disparities emerged in the 1990s and has rapidly grown in scope and content. This introduction provides an overall frame for the articles presented in this special issue. The frame includes an overview of how health disparities and health equities have been defined and examined in previous research, challenges in conducting health disparities research, and the progress that has been made. The articles in this special issue address the challenges of health disparity research through new conceptual models, the expansion of diseases and health behaviors wherein disparities occur, intersectionality theory, innovative research designs, and workforce training. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Lessons Learned: Challenges and Strategies for Conducting Family-Based Intervention Research in Juvenile Justice Settings.

Greater than 60% of youths in the juvenile justice system have a diagnosable mental health disorder, with substance use-related and addictive disorders being among the most common mental health disorders.1 Research studies have shown that family-based interventions targeting substance use-related and addictive disorders have two to nine times greater effect sizes compared with individual-based interventions.2 Family-based interventions, most notably, functional family therapy,3 multidimensional family therapy,4 and multisystemic therapy,5 have been shown to reduce substance use among justice-involved youths. Given the complex and multiple demands facing justice-involved youths, conducting family-based research within juvenile justice populations can be challenging. This article provides insights into the operational challenges and innovative strategies to address these challenges to conduct family-based intervention research with reentry youths.

Trauma, Family Factors and the Mental Health of Homeless Adolescents.

Family factors, such as poor family functioning and trauma, have been associated with negative outcomes for homeless adolescents. Further study is needed to better understand how family factors and trauma jointly relate to mental health problems and externalizing behaviors among homeless adolescents. Structural equation modeling was used to examine the influence of trauma (encompassing traumatic events experienced prior to, and after, becoming homeless) and family factors (poor family functioning and family conflict) on mental health problems and externalizing behaviors (substance use, delinquent behaviors, and sexual risk) among 201 homeless adolescents, ages 12 to 17 years. Trauma, poor family functioning, and family conflict significantly predicted greater mental health problems, delinquent behaviors, high-risk sexual behaviors and substance use. Overall, the findings suggest that family factors appear to be key to understanding mental health problems and externalizing behaviors among homeless adolescents. Implications, limitations and future directions are addressed.