Immunotherapy: RAPID ACCESS TO VIRUS-SPECIFIC T CELLS FOR ADOPTIVE IMMUNOTHERAPY FOR COMPASSIONATE USE IN AUSTRALIA

Background & Aim: Adoptive T cell immunotherapy holds great promise for the treatment of viral complications. Our group has been developing and trialling virus-specific T cell therapies for more than 20 years. Recently, we have generated a repository of multi-virus-specific T cells for our clinical trials. Unfortunately, for many patients with viral complications, there is no suitable trial through which to access these therapies. In Australia, the Therapeutic Goods Administration has a Special Access Scheme (SAS) to enable provision of unapproved therapies for compassionate use. Our research group is now a leading Australian provider of "off-the-shelf" and custom-grown allogeneic virus-specific T cells to hospitals for patients with no other treatment options. Methods, Results & Conclusion(s): We have generated a repository of multi-virus-specific T cells from 20 healthy donors, with up to 150 doses of T cells per donor generated from a single blood sample. Each product batch is thoroughly characterised in terms of viral antigen specificity, HLA restriction and alloreactivity. These T cells target a combination of Epstein-Barr virus, cytomegalovirus, BK polyomavirus, John Cunningham virus and adenovirus epitopes. We have also generated a repository of SARS-CoV-2-specific T cells and occasionally grow custom patient-specific batches of T cells from nominated donors, on request. Since 2008, we have provided virus-specific T cells to 15 hospitals across Australia, and the volume of supply requests has significantly increased in recent years, as clinicians have gained interest in adoptive immunotherapy. In 2022, we provided T cells for 26 patients via the SAS. The majority were experiencing post-transplant complications, including cytomegalovirus disease, BK virus-associated haemorrhagic cystitis and post-transplant lymphoproliferative disorder. Through our clinical trials, we have developed rigorous processes for T cell therapy manufacture and characterisation, in addition to a computer-based selection algorithm, which we apply to SAS cases. As these cases are not part of a clinical trial, concomitant therapy varies, and monitoring is not uniform. However, we have received reports of clinical benefit from adoptive T cell therapy. These include cases of reduction in viral load, improvement in symptoms, and complete resolution of infection. We believe that these promising T cell therapies should be available to hospitals through a nationally funded centre for cellular therapies for critically ill patients.Copyright © 2023 International Society for Cell & Gene Therapy

Experience of Research Ethics Committees in Africa during the COVID-19 Pandemic (preprint)

Background and objective : Globally, COVID-19 has caused a number of challenges including the functioning of research ethics committees (RECs) with the impact being expected to be more pronounced in resource-limited countries. The objective of this study was to describe RECs' functions and challenges experienced during the pandemic in Africa.Method A cross-sectional study covering Anglophone and Francophone countries in Africa was done. Data was collected using an online Google form questionnaire. The link to the form was sent to REC chairs and secretaries to fill in online. Descriptive data analysis was done using Microsoft Excel and SPSS version 25.Result A total of 98 study participants (50 members and 48 chairs) responded from 16 African countries. The mean (standard deviation) age of REC members was 47 (12) and over half of them, 27 (54%) were female. Most REC members and chairs were physicians, while 48% of RECs were affiliated with academic institutes. Ninety percent of REC chairs reported that their REC was accredited; however, only three had recognition by Strategic Initiative for Developing Capacity in Ethics Review (SIDCER). RECs reported reviewing COVID-19 related protocols. In 2019, chairs reported RECs reviewing 5,860 protocols with a 13% increment in 2020. During the COVID-19 pandemic, there was an increment in protocol amendment (79%), deviation (29%), and early protocol termination (25%). Most (96%) RECs followed COVID-19 prevention institutional policies including limiting face-to-face meetings and shifting to virtual platforms. RECs challenges in reviewing COVID-19 related proposals were issues related to risk/benefit, scientific design, and informed consent.Conclusion The COVID-19 pandemic has impacted the functions of RECs in Africa, both in the increase in the volume of proposals for review and presenting new ethical challenges including in risk-benefit analysis. There is a need to strengthen RECs in the region through different mechanisms, by building their capacity through initiatives like the SIDCER recognition program. To strengthen African RECs in a sustainable manner, some of the interventions could be establishing National and regional REC databases, and putting in place continuous training opportunities preferably through an online platform.

Psychosocial experiences of people living with advanced colorectal cancer: A qualitative exploration

Aims: Survival of people with advanced colorectal cancer (CRC) can be prolonged through treatment pathways including cytoreductive surgery and hypothermic intraperitoneal chemotherapy (CRS-HIPEC), pelvic exenteration, liver resection, and palliative chemotherapy without surgery. Virtually no qualitative research has compared the experiences and needs of advanced CRC survivors who receive these treatments. This study aims to fill this gap. Methods : Adult survivors of CRC who have undergone the aforementioned treatments are being recruited 0.5-2 years post-surgery or, for palliative chemotherapy participants, 0.5-2 years post-diagnosis of advanced CRC. Recruitment will continue until approximately N = 40 or data saturation is reached. Quantitative data include: demographic and clinical data, Functional Assessment of Cancer Therapy - Colorectal (FACT-C), Distress Thermometer, and Comprehensive Score for Financial Toxicity (COST). Quantitative data will undergo descriptive analysis to characterise the sample. All participants will participate in a qualitative semi-structured telephone interview exploring quality of life, employment, finances, stigma, supportive care needs, social functioning, perceptions of survivorship, and impacts of COVID-19. Interviews are analysed via the framework approach of thematic analysis. Results : Preliminary analysis of 36 interviews (n = 10 CRS-HIPEC, n = 10 pelvic exenteration, n = 9 liver resection, n = 7 palliative chemotherapy) reveals some advanced CRC survivors report post-surgical complications and chemotherapy-induced peripheral neuropathy, which can limit physical activity. CRC impacted some participants' psychosocial well-being ability to work, and sense of identity. Participants reportedly manage these impacts through distraction, positive reframing, and contact with other CRC survivors. Most participants appeared satisfied with their cancer treatment teams. Some viewed GPs as important healthcare coordinators. COVID-19 made some participants more cautious when leaving the house. Telehealth was considered less personal, but convenient. Conclusions : The study's findings will help guide development of interventions to improve the survivorship experience of patients who receive treatment for advanced CRC. This may include an information booklet, patient-reported outcome measure, clinical pathway, or targeted intervention.

Public Mobility Data Enables COVID-19 Forecasting and Management at Local and Global Scales

Policymakers everywhere are working to determine the set of restrictions that will effectively contain the spread of COVID-19 without excessively stifling economic activity. We show that publicly available data on human mobility — collected by Google, Facebook, and other providers — can be used to evaluate the effectiveness of non-pharmaceutical interventions and forecast the spread of COVID-19. This approach relies on simple and transparent statistical models, and involves minimal assumptions about disease dynamics. We demonstrate the effectiveness of this approach using local and regional data from China, France, Italy, South Korea, and the United States, as well as national data from 80 countries around the world.

Psychosocial outcomes and QoL in advanced colorectal cancer survivors: A qualitative exploration

Background: Approximately 18% of colorectal cancer (CRC) diagnoses are advanced cancer, whereas 30%-40% of patients develop recurrence after treatment with curative intent. More modern treatments enable longer survival for people with advanced CRC, including cytoreductive surgery and hypothermic intraperitoneal chemotherapy (CRS-HIPEC), pelvic exenteration, liver resection, and palliative chemotherapy without surgery. Yet, virtually no qualitative research has compared the perspectives and quality of life (QoL) experiences of survivors of these different treatments. This study aims to fill this gap. Methods: Approximately N = 40 adult survivors of CRC are being recruited from two major Australian hospitals 0.5-2 years posttreatment or post-diagnosis. All participants will complete the Functional Assessment of Cancer Therapy - Colorectal (FACT-C), Distress Thermometer and Comprehensive Score for Financial Toxicity (COST) questionnaires. Questionnaire data, participant demographics and clinical data will undergo descriptive analysis to characterise the sample. Participants will participate in a qualitative semi-structured telephone interview, analysed via the framework approach of thematic analysis. Qualitative interviews explore QoL, survivorship experiences, employment and finances, supportive care needs, stigma and social functioning and impacts of COVID-19. Results: Preliminary analysis of 30 interviews (n=10 CRS-HIPEC, n=9 pelvic exenteration, n = 5 liver resection, n = 6 palliative chemotherapy) reveals someadvancedCRCsurvivors report post-surgical complications and chemotherapy-induced peripheral neuropathy, which can limit physical activity and daily functioning. Participants reportedly manage these through distraction, positive reframing and contacting other CRC survivors. Most participants appeared satisfied with their cancer treatment teams. Some viewed their GPs as important coordinators in their health care. Some CRC survivors viewed the change to telehealth due to COVID-19 as less personal;however, rural/regional participants prefer its convenience. Conclusions: The study findings will help guide development of interventions to improve the survivorship experience of patients who receive treatment for advanced CRC. This may include an information booklet, patient-reported outcome measure, clinical pathway or targeted intervention.

Public Mobility Data Enables COVID-19 Forecasting and Management at Local and Global Scales (preprint)

Policymakers everywhere are working to determine the set of restrictions that will effectively contain the spread of COVID-19 without excessively stifling economic activity. We show that publicly available data on human mobility --- collected by Google, Facebook, and other providers --- can be used to evaluate the effectiveness of non-pharmaceutical interventions and forecast the spread of COVID-19. This approach relies on simple and transparent statistical models, and involves minimal assumptions about disease dynamics. We demonstrate the effectiveness of this approach using local and regional data from China, France, Italy, South Korea, and the United States, as well as national data from 80 countries around the world.