Holes, Patches and Multiple Hats: The Experiences of Parents of Students with Special Education Needs Navigating At-Home Learning During COVID-19

In the spring of 2020, schools across Canada and beyond closed as a public health measure to address the growing COVID-19 global pandemic. The abrupt shift to at-home learning necessitated, for many children, significant engagement by parents and family members. This chapter brings forward the perspectives of 36 Canadian parents of students with special education needs as they supported the learning of their children during school closures. Analyses of in-depth interviews revealed interrelated influences of community, family and school supports, parent efficacy and mental health. Stories shared by parents highlighted the weaknesses of school systems that were exposed when the first wave of the pandemic hit. Lessons learned include the need to develop and sustain networks of support for families of students with special education needs, particularly working mothers, and the importance of building authentic and productive partnerships between families and schools. © The Editor(s) (if applicable) and The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022

Perspectives of Parents of Children With Special Education Needs: Self-Efficacy and School Supports During COVID-19 School Closures

in the spring of 2020. Schools in most Canadian provinces closed physically due to COVID-19, and remote-learning options were quickly developed to ensure continued education for students. Many students with special educational needs, who typically benefit from a range of supports from school, became reliant on parents to provide means of access to and participation in remote learning. Using an online survey, we explored the perceptions of 263 Canadian parents of children with special education needs with regard to their self-efficacy and supports from schools. We conducted multiple linear regression analyses for each of three dependent variables (academic supports, parent self-efficacy, and social-emotional supports);independent variables included student grade level, education placement, and total school-provided supports prior to the pandemic. Findings indicated that most parents engaged in remote learning and lacked confidence in their ability to support the learning of their child. Parent self-efficacy was related to social-emotional supports from schools and not to academic supports. Parents of children in elementary grades, and of those who had received more supports from school prior to COVID-19, reported feeling better supported in social-emotional areas by the school. Schools should explore ways of building strong collaborative relationships between educators and parents, as well as continuing to find ways of supporting families and students in both in and out-of-school places. The pandemic, and school-building closures, have reminded us how partnerships between parents and schools are crucial for the well-being of all involved. © 2021,Exceptionality Education International. All Rights Reserved.

First-in-human CAR T targets MUC1 transmembrane cleavage product

Purpose: To develop a MUC1-targeted CAR T that recognizes the growth factor receptor form, MUC1∗, does not bind full-length MUC1, hits a wide range of solid tumor cancers, binds to little or no normal tissues, and effectively kills tumor cells. Methods: Because MUC1 is expressed on normal epithelial tissues, we needed to develop an antibody that would only bind to the aberrant, cancerous form - MUC1∗. MUC1∗ (muk1 star) is the transmembrane portion that remains after MUC1 is enzymatically cleaved and the bulky tandem repeat domain is shed from the cell surface. MUC1∗ is a growth factor receptor that is activated by ligand-induced dimerization of its truncated extracellular domain. Via a novel screen we identified antibodies that bind to a specific conformation within the ectopic epitope that is created when MUC1 is cleaved to MUC1∗ by enzymes secreted by the tumor microenvironment. This set of antibodies competitively inhibit the binding of onco-embryonic growth factor NME7AB to the cancerous form of MUC1∗. We incorporated one of these cancer-specific antibodies into a CAR T. Results: huMNC2-CAR44 is in a 1st-in-human clinical trial [NCT04020575] for metastatic breast cancers, currently being performed at the Fred Hutchinson Cancer Research Center. Our IND-enabling studies showed that huMNC2-scFv bound robustly to 95% of breast cancer tissues, 83% ovarian cancers, 78% pancreatic cancers and 71% of lung cancer tissues, but showed little to no binding to normal tissues. In co-culture experiments, huMNC2-CAR44 T cells did not kill MUC1∗ negative cells, even if they expressed full-length MUC1, and the presence of MUC1∗ negative cells did not elicit a cytokine response from the CAR T cells. In vivo, huMNC2-CAR44 T cells inhibited or completely obliterated a variety of MUC1∗ positive solid tumors in NSG mice (n≥400). The human CD8+ huMNC2-CAR44 T cells expanded in animals as tumors shrunk, whereas the untransduced T cells did not. Clinical trial was slowed by COVID-19, as Seattle was the first hotbed of the virus. Thus far, there have been no serious adverse events attributed to the CAR T therapy. Even at the lowest dosage, patients have had robust CAR T cell expansion and have also had measurable signs of efficacy. Conclusions: MUC1∗ is the predominant form of MUC1 on cancerous tissues. Antibodies that bind to a specific conformation within the ectopic growth factor binding site in the MUC1∗ extra cellular domain are tumor selective. CAR T cells incorporating these antibodies are highly effective against solid tumors in animals. Robust staining of cancerous tissues and minimal to no staining of normal tissues predicts a large therapeutic window for huMNC2-CAR44 T cell dosing. Early patient responses appear to fulfill the predictions of the IND-enabling studies. We have now developed a cryopreservation formulation which enables shipping frozen product to additional clinical sites for bedside thaw and infusion. The trial is currently enrolling patients.

Impact of COVID-19 on study sites: Survey analysis from the noninterventional POLARIS study

Background: The COVID-19 pandemic is negatively affecting patient enrollment, therapy administration, and patient visits in breast cancer clinical trials worldwide. COVID-19 may have a lasting impact on how clinical trials are conducted, and guidelines are necessary to inform trial design and patient safety. While many groups and journals have recently published guidelines, including NCCN, ESMO, IQVIA, and Lancet Oncology, there is no consensus on how to treat patients in the current environment. Understanding and quantifying the impact of the pandemic on clinical study sites will help inform the rational development of a consensus approach. The goal of this survey was to gather site-level data on the impact of COVID-19 from clinical sites participating in the POLARIS study (NCT03280303), an ongoing, prospective, real-world, noninterventional study in patients with hormone receptorpositive/ human epidermal growth factor receptor 2-negative advanced breast cancer receiving palbociclib plus endocrine therapy. Methods: Two rounds of questionnaires were sent to investigators at POLARIS study sites: 1 via email March 26-27, 2020, and 1 via telephone from April 30-May 20, 2020. The questions on COVID-19 impact and management are shown in the Table. Results: Eighty of 122 POLARIS study sites contacted responded to the March questionnaire, and 86 responded to the April-May questionnaire. In March, 33% (26/80) of the surveyed population were working predominantly remotely, 26% (21/80) were working both onsite and remotely, and 3 1% (25/80) were working onsite. Approximately 24% of sites reported delayed data entry. The option of telemedicine or office visits was offered to subjects at approximately 73% (58/80) of sites, and 11% (9/80) of sites were restricted to telemedicine visits. In April-May, 36% (31/86) of respondents reported an impact on study management and 64% (55/86) reported no impact. Approximately 94% (81/86) of surveyed sites felt they were able to maintain clinical studies despite the challenges due to COVID-19, and 79% (68/86) of sites had the option for telemedicine and/or office visits, while 18% (16/86) had no telemedicine alternative. In April-May, 38% of sites reported an impact on patient visits. Conclusion: Although these findings must be interpreted with caution due to the limitations of survey studies, the results suggest that approximately 1/3 of the study sites will experience an impact on their responsiveness to correspondence, timely data entry, and subject management due to the COVID-19 pandemic. Telemedicine may be used to mitigate the effect of the pandemic on clinical trial execution.