RESUMO
BACKGROUND: ALL_EARS@UoS is a patient and public involvement and engagement (PPIE) group for people with lived experience of hearing loss. The purpose of the group is to share experiences of hearing loss and hearing healthcare, inform research and improve services for patients at University of Southampton Auditory Implant Service. A year after inception, we wanted to critically reflect on the value and challenges of the group. Four members of ALL_EARS@UoS were recruited to an evaluation steering group. This paper reports the evaluation of the group using the UK Standards for Public Involvement. METHODS: An anonymous, mixed-methods questionnaire was co-designed and shared with members of ALL_EARS@UoS using an online platform. The questionnaire was designed to capture satisfaction, individual feedback through free-text answers, and demographic information. Descriptive statistics have been used to express the satisfaction and demographic data. Reflexive thematic analysis has been used to analyse the free-text responses. Group engagement and activity data over time were monitored and collected. RESULTS: The questionnaire response rate was 61% (11/18). Areas identified as strengths were 'Communication' and 'Working together'. Five themes were developed from the thematic analysis; (1) Increased knowledge and awareness around the topic of hearing health for group members and wider society, (2) supporting research, (3) inclusivity within the group, (4) opportunity to make a difference for people in the future and (5) running of the group/group organisation. The data highlighted the value and challenges of PPIE. Members described feeling listened to and appreciation of being able to share experiences. Time of day and meeting format were identified as challenges as they affected who could attend the meetings. The ability to secure and maintain sufficient funding and time to support inclusive and diverse PPIE activities is a challenge for researchers. CONCLUSIONS: We have identified how PPIE added value to both group members and researchers, emphasising the true benefit of PPIE. We have highlighted challenges we are facing and our plan to tackle these. We aim to continue to develop and sustain a group that reflects the diversity of the Deaf/deaf or hard of hearing community and of our local community.
RESUMO
BACKGROUND: CD73 is widely expressed on immune cells playing a critical role in immunomodulatory functions including cell adhesion and migration, as a costimulatory molecule for T cells and in production of adenosine. The function of CD73 expressed on B cells has not been fully characterized. Mupadolimab is an anti-human CD73 antibody that activates B cells. We evaluated the characteristics of this antibody and its effects on immune cells in vitro and in vivo. METHODS: Mupadolimab binding to CD73, inhibition of CD73 enzymatic activity, and effects on lymphocyte activation were evaluated in vitro by measuring changes in immunophenotype by flow cytometry. Cryogenic-transmission electron microscopy was used to determine epitope binding. Effects on human B cells in vivo were evaluated in immunodeficient NSG-SGM3 mice immunized with SARS-CoV-2 and influenza viral antigens. Safety and immune effects were evaluated in the completed dose escalation portion of a phase 1 trial conducted in patients with cancer. RESULTS: Mupadolimab binds to a unique epitope on CD73POS B cells resulting in their activation and differentiation through B cell receptor signaling pathways. Mupadolimab induces expression of CD69, CD83, CD86 and MHC class II on B cells along with morphological transformation into plasmablasts and expression of CD27, CD38 and CD138. These effects are independent of adenosine. Mupadolimab binds to the N-terminal of CD73 in the closed position and competitively inhibits substrate binding. Mupadolimab enhanced antigen specific antibody response to SARS-CoV-2 spike protein and influenza hemagglutinin in humanized mouse models. Mupadolimab was evaluated as a monotherapy in a phase 1 trial (NCT03454451) in 34 patients with advanced cancer and demonstrated binding to CD73POS circulating cells and transient reduction in the number of B cells, with return of CD73NEG B cells with memory phenotype. No dose-limiting toxicities or changes in serum immunoglobulins were seen. CONCLUSIONS: Mupadolimab activates B cells and stimulates the production of antigen specific antibodies. The effects in patients with cancer suggest that activated, CD69POS B cells redistribute to lymphoid tissues. Minor tumor regression was observed in several patients. These results support further investigation of mupadolimab as an immunotherapy for cancer and its potential use as a vaccine adjuvant. TRIAL REGISTRATION NUMBER: NCT03454451.
