An off-the-shelf CD2 universal CAR-T therapy for T-cell malignancies

T-cell malignancies are associated with frequent relapse and high morbidity, which is partly due to the lack of effective or targeted treatment options. To broaden the use of CAR-T cells in pan T-cell malignancies, we developed an allogeneic universal CD2-targeting CAR-T cell (UCART2), in which the CD2 antigen is deleted to prevent fratricide, and the T-cell receptor is removed to prevent GvHD. UCART2 demonstrated efficacy against T-ALL and CTCL and prolonged the survival of tumor-engrafted NSG mice in vivo. To evaluate the impact of CD2 on CAR-T function, we generated CD19 CAR-T cells (UCART19) with or without CD2 deletion, single-cell secretome analysis revealed that CD2 deletion in UCART19 reduced frequencies of the effector cytokines (Granzyme-B and IFN-γ). We also observed that UCART19ΔCD2 had reduced anti-tumor efficacy compared to UCART19 in a CD19+NALM6 xenograft model. Of note is that the reduced efficacy resulting from CD2 deletion was reversed when combined with rhIL-7-hyFc, a long-acting recombinant human interleukin-7. Treatment with rhIL-7-hyFc prolonged UCART2 persistence and increased survival in both the tumor re-challenge model and primary patient T-ALL model in vivo. Together, these data suggest that allogeneic fratricide-resistant UCART2, in combination with rhIL-7-hyFc, could be a suitable approach for treating T-cell malignancies

The Lack of an Association Between Adolescent Friends\u27 Prejudices and Stereotypes

Four hundred twenty-six white male and female, ninth and eleventh graders completed questionnaires that evaluated race, homosexual, HIV/AIDS, and fat prejudice, and sex-role stereotyping. A factor of intolerance was determined using all five scales. Regression analyses evaluated whether the association of prejudice attitudes among friends was conditional on friendship reciprocity, closeness, having one versus two friends, congruity of friends’ prejudices, authoritative parenting, and degree of prejudice of the target adolescent. Friends’ prejudices and stereotypes were not associated. Possible explanations were offered, including: discussions of prejudice and stereotyping may be rare among students; adolescents assume that their friends have similar attitudes to their own and thus don’t question apparent differences; and adolescents may influence each other’s behaviors, but not prejudices or stereotypes

Modeling the Effects of Spirituality/Religion on Patients’ Perceptions of Living with HIV/AIDS

Spirituality/religion is an important factor in health and illness, but more work is needed to determine its link to quality of life in patients with HIV/AIDS.To estimate the direct and indirect effects of spirituality/religion on patients’ perceptions of living with HIV/AIDS.In 2002 and 2003, as part of a multicenter longitudinal study of patients with HIV/AIDS, we collected extensive demographic, clinical, and behavioral data from chart review and patient interviews. We used logistic regression and path analysis combining logistic and ordinary least squares regression.Four hundred and fifty outpatients with HIV/AIDS from 4 sites in 3 cities.The dependent variable was whether patients felt that life had improved since being diagnosed with HIV/AIDS. Spirituality/religion was assessed by using the Duke Religion Index, Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being—Expanded, and Brief RCOPE measures. Mediating factors included social support, self-esteem, healthy beliefs, and health status/health concerns.Approximately one-third of the patients felt that their life was better now than it was before being diagnosed with HIV/AIDS. A 1-SD increase in spirituality/religion was associated with a 68.50% increase in odds of feeling that life has improved—29.97% due to a direct effect, and 38.54% due to indirect effects through healthy beliefs (29.15%) and health status/health concerns (9.39%). Healthy beliefs had the largest effect on feeling that life had improved; a 1-SD increase in healthy beliefs resulted in a 109.75% improvement in feeling that life changed.In patients with HIV/AIDS, the level of spirituality/religion is associated, both directly and indirectly, with feeling that life is better now than previously. Future research should validate our new conceptual model using other samples and longitudinal studies. Clinical education interventions should focus on raising awareness among clinicians about the importance of spirituality/religion in HIV/AIDS