Citations

Mucin-1 (MUC1) is a highly relevant antigen for cancer vaccination due to its overexpression and hypo-glycosylation in a high percentage of carcinomas. To enhance the immune response to MUC1, our group has developed C3-liposomes that encapsulate the MUC1 antigen along with immunostimulatory compounds for direct delivery to antigen-presenting cells (APCs). C3-liposomes bind complement C3, which interacts with C3-receptors on APCs, resulting in liposomal uptake and the delivery of tumor antigens to APCs in a manner that mimics pathogenic uptake. In this study, MUC1 and Toll-like receptor (TLR) agonists were encapsulated in C3-liposomes to provoke an immune response in transgenic mice tolerant to MUC1. The immune response to the C3-bound MUC1 liposomal vaccine was assessed by ELISA, ELISpot, and flow cytometry. Co-administering TLR 7/8 agonists with MUC1 encapsulated in C3-liposomes resulted in a significant antibody response compared to non-encapsulated MUC1. This antibody response was significantly higher in females than in males. The co-encapsulation of three TLR agonists with MUC1 in C3-liposomes significantly increased antibody responses and eliminated sex-based differences. Furthermore, this immunization strategy resulted in a significantly increased T cell-response compared to other treatment groups. In conclusion, the co-delivery of MUC1 and TLR agonists via C3-liposomes greatly enhances the immune response to MUC1, highlighting its potential for antigen-specific cancer immunotherapy.

Abstract Objective Parents of youth with chronic pain report psychosocial difficulties, yet treatment often focuses on improving their child’s functioning and pain. This study evaluated changes in parents’ social and emotional functioning and explored predictors of change, as they completed a parent-focused intervention while their child was enrolled in an intensive interdisciplinary pain treatment (IIPT) program. Methods Parents (n = 69) completed questionnaires at baseline and weekly (average duration of 4 weeks) during their child’s participation in IIPT. Parents engaged in 3 groups per week providing education, therapeutic art, and psychotherapy (3 hr/week total). Results At baseline, 38% of parents reported scores in the clinically elevated range for at least 1 psychosocial variable. Linear mixed modeling for the full sample indicated reduced parent anxiety (t = −2.72, p <.01) and depression (t = −3.59, p <.001), but not increased emotional support (t = 1.86, p >. 05) or reduced social isolation (t = −1.20, p >.05). For parents with at least moderately elevated psychosocial concerns, statistically significant improvements were observed for all 4 outcomes (all p’s<.01). Psychological flexibility, cognitive reappraisal, and emotional suppression were found to be related to changes in parent outcomes (anxiety, depression, isolation, and support). Conclusions Findings support the benefit of parent-focused interventions in addition to child-focused interventions. Many parents of youth participating in IIPT had elevated scores for at least 1 psychosocial concern at baseline. Brief, parent-focused intervention including psychoeducation, therapeutic art, and psychotherapy targeting mindfulness, acceptance, and values had a significant impact on these parents, particularly those with greater struggles at baseline.