Adoptive cell immunotherapy (ACT) with engineered T cells has shown impressive efficacy against some cancers, particularly CD19+ leukemias. However, ACT efficacy in solid tumors can be limited by restrictive tumor microenvironments (TMEs), with increased inhibitory signals, reduced T cell infiltration/accumulation, and inadequate metabolic substrates. We engineer T cells with novel switch receptors that combine an inhibitory ectodomain with a costimulatory signaling endodomain, to “replace a break with an accelerator”. FasL is a death receptor ligand that is overexpressed in the majority of human TMEs and can protect tumor cells from immunity by giving T cells inhibitory signals upon binding. We engineered a Fas-4-1BB switch receptor to convert the Fas death signal to a costimulatory 4-1BB signal and demonstrated enhanced Fas switch-receptor-T cell in vivo persistence and therapeutic efficacy in a murine pancreatic cancer model (KPC). We developed new switch receptor candidates by combining CD200R, an inhibitory signaling receptor, ectodomain with various co-stimulatory endodomains. Our aim is to screen for CD200R switch receptors that exhibit the best expression on T cells, best ability in tumor-lysis and proliferation with the least exhaustion in TMEs, and test the best candidates in KPC models. We are able to transduce mouse T cells to express our CD200R constructs, which is verified by flow cytometry, and ready to start in vitro killing assay to assess their ability in tumor-lysis. This T cell engineering strategy may help overcome the restrictive TMEs, catalyze an endogenous immune response, and greatly improve T cell anticancer efficacy.

Systemic racism is a widespread issue in America that has an adverse impact on the psychological well-being of ethnic minority populations. Although there is significant research on the importance of addressing racism in psychotherapy and adopting culturally humble interventions, limited studies exist on the frequency with which clinicians ask Clients of Color about experiences of race or racism. Thus, this study examines the percentage of community mental health clinicians who report intent to discuss issues of race or racism with Clients of Color. In this study, surveys were distributed to participants (N = 138) from a statewide Cognitive Behavioral Therapy training initiative in Washington state. Clinicians rated their level of agreement with 11 statements describing their intentions of discussing race/racism with clients on a 7-point Likert-type scale. We will employ descriptive statistics to assess the frequency with which clinicians intend to address issues of race or racism with Clients of Color. The existing limitations of this study include the predominant use of self-report questionnaires after receiving CBT+ (Cognitive Behavioral Therapy) training. Ultimately, our findings can highlight if clinicians initiate discussions surrounding race or racism with Clients of Color, which can inform researchers if more support is needed in the form of resources or additional training for clinicians to effectively approach discussions of race or racism.

Ever since the COVID-19 outbreak, hate crimes and violence towards minoritized groups such as Black and Asian people have surged. Consequently, Black, Indigenous, and People of Color (BIPOC) continue to face several mental health challenges as well as inaccessibility to mental health care. The literature suggests that culturally responsive psychotherapy can improve BIPOC clients’ clinical outcomes. Thus, this study examines the actions community mental health (CMH) clinicians have taken to better serve BIPOC clients. Data came from a Washington State-funded cognitive-behavioral therapy training initiative (CBT+) in 2020 - 2021. CMH clinicians and supervisors attended a virtual CBT training followed by six months of expert consultation and completed pre-training and post-consultation surveys. In the surveys, CMH clinicians reported on the frequency of performing certain actions to better serve their BIPOC clients (e.g., discuss issues of race or racism with BIPOC clients) using a 5-point Likert Scale ranging from 0 (Never) to 5 (Always). We conducted descriptive statistics to summarize clinicians’ responses. Our analyses showed that clinicians most frequently incorporated the following actions when working with BIPOC clients: “consider the client's ethnicity” and “the use of bilingual staff or interpreters for those whose English is not their first language.” On the other hand, clinicians appeared to rarely collaborate with natural community healers, spiritual healers, clergy, etc., as part of their service delivery. Our findings suggest that CMH clinicians have taken several actions to thoughtfully consider and incorporate BIPOC clients’ backgrounds and context into treatment delivery. However, certain CMH clinicians' actions to better serve BIPOC clients occur more frequently than others. Future research should better understand which culturally responsive actions are most helpful in helping BIPOC clients’ experiences in CMH.