Purpose-This study aims to introduce the University Handprint Framework-a novel method for quantifying the external positive impacts ("handprints") of sustainability actions undertaken by higher education institutions. It aims to fill a critical gap in current sustainability tracking systems by enabling universities to measure their contributions to societal and environmental outcomes beyond campus boundaries. Design/methodology/approach-The study presents a case study of a project-based sustainability course that partnered students with external organizations to implement climate-related solutions. The study calculated the university's potential handprint associated with the course and informed the development of the University Handprint Framework. Data challenges, such as availability, tracking, attribution and double counting of emissions, were addressed in the method's development to ensure methodological rigor. Findings-This study results revealed that the course enabled partner organizations to reduce greenhouse gas emissions by an estimated 7.04E + 05 kg CO2-eq, which demonstrated a quantifiable, university-enabled carbon handprint beyond campus boundaries. Practical implications-The framework offers universities a practical tool to highlight their broader societal contributions and can inform policy, reporting and investment in sustainability education and research. Given universities' pivotal role in research dissemination, sustainability education and climate change mitigation, showcasing these positive impacts is essential. Originality/value-This is the first known framework tailored to higher education that enables structured quantification of both potential (ex ante) and realized (ex-post) handprints. It complements existing tools and adds a new dimension to sustainability planning and impact tracking in academia.
7022 Background: Glofitamab is a CD20xCD3 T-cell engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells in patients (pts) with relapsed or refractory non-Hodgkin Lymphoma. We characterized mechanisms driving CD20 loss in pts from a Phase I/II trial (NP30179) receiving Glofitamab monotherapy for Relapsed/Refractory Large B-cell lymphoma (R/R LBCL). Methods: Pts with LBCL and ≥2 prior therapies received obinutuzumab pretreatment followed by fixed-duration Glofitamab at the approved dose in phase I/II trial NP30179 ( NCT03075696 ) (Dickinson, et al. N Engl J Med 2022). Tumor biopsies were collected prior to treatment (Baseline, BL) in 128 pts, during treatment (tx) or at progression (PD) in 11 pts. The proportion of CD20+ tumor cells was determined by immunohistochemistry (IHC) using a dual CD20+ PAX5+ assay. Expression of MS4A1 , the gene encoding CD20, was measured by RNA-sequencing (RNA-seq) in 105/139 biopsies. MS4A1 mutation profiling was performed by next-generation sequencing on Cell-free circulating tumor DNA (ctDNA) from 133 pts. We subsequently characterized the functional consequences of identified mutations in vitro. Results: CD20 levels evaluated by IHC were high (>75% CD20+ tumor cells) in 110/128 BL biopsies. At BL, CD20 loss (<5% CD20+ tumor cells) was seen in 4/128 (3.1 %) biopsies. For 11 pts with BL and on-tx or at-PD biopsies, 7/11 (63.6%) pts presented CD20 loss on-tx/at-PD and 4/11 (36.4%) did not. Evaluation of gene expression profile showed a good correlation between CD20 gene and protein expression. Among the 7 pts with CD20 loss on-tx/at-PD biopsies, there were 4 biopsies with available gene expression data, and decreased CD20 expression was identified in 2/4. Evaluation of CD20 mutation revealed 11/134 (8.2%) pts harbored 16 MS4A1 mutations at BL or on-tx/at-PD. IHC data were available for 8/11 pts at BL where 2/8 presented CD20 loss (<5% CD20+ tumor cells), and for 1 pt at-PD who presented CD20 loss. 12/16 mutations were not previously reported. We characterized 14 mutations in vitro and subsequently demonstrated that 8 frameshift or deletion mutations lead to truncation of the protein, and 4 missense mutations lead to disruption in the transmembrane domain of CD20. These 12 mutations lead to loss of intracellular and extracellular CD20 expression, and abrogation of Glofitamab-mediated cytotoxicity in vitro. Conclusions: In pts with R/R LBCL treated with Glofitamab, loss of tumor antigen CD20 expression is one resistance mechanism to Glofitamab. Genetic alterations (fs, del or missense mutations) and transcriptional downregulation can contribute to loss of CD20 expression and they were both observed in pts treated with Glofitamab. Acknowledgments: The NCT03075696 study is sponsored by F. Hoffmann-La Roche Ltd.
7042 Background: In recent years, bispecific T cell Engagers (BsTCE) targeting CD3 and CD20 have emerged as a potent new class of therapeutics for NHL; however, a subset of patients still experience relapsed or refractory disease. Patients undergoing treatment with BsTCEs could benefit from longitudinal screening via liquid biopsy to identify baseline (primary) and treatment-induced (acquired) resistance mutations and tailor treatment accordingly. Here we present the results from a pilot study screening patients treated with Glofitamab (CD20xCD3) using a single gene Primer Extension Target Enrichment (PETE) strategy for MS4A1 (CD20 gene) in liquid biopsies. Methods: Our pilot study was conducted using libraries from the plasma of 134/155 patients with relapsed or refractory large B cell lymphoma (r/r LBCL) who underwent Glofitamab treatment at approved dose in the phase I/II trial NP30179 ( NCT03075696 ) (Dickinson, et al. N Engl J Med 2022), and paired PBMC/PDB available in 91 cases. Primers were designed against the coding regions of the MS4A1 gene. Enrichment was performed using a workflow optimized for the detection of somatic variants in cell-free DNA isolated from plasma. Results were analyzed using a modified AVENIO circulating tumor (ct) DNA (Roche; For Research Use Only) analysis workflow. Variants detected by the analysis pipeline were further filtered based on inclusion criteria: allele fraction > 0.1%, rarity in the cohort, impact on protein function in silico , and if sample was available, absence in germline. Tumor burden as assessed by ctDNA was obtained from retrospective sequencing data. Response to treatment was assessed by PET/CT using the Lugano Criteria. Results: Using inclusion criteria a total of 11/134 (8.2%) patients were identified with a total of 16 unique MS4A1 candidate mutations at baseline or during treatment. The Best Overall Investigator Response (BOR) was progressive disease (PD) for 7 patients and partial metabolic response (PR) for 4 patients. All patients with BOR PR experienced disease progression before treatment completion. Sufficient samples were available to demonstrate expansion of the candidate mutation by the end of treatment (EOT) timepoint for 5 patients. Four of the identified mutations were previously reported in the literature, the remaining mutations were novel, and in vitro characterization demonstrated their functional impact. Conclusions: This work identifies known and novel mutations in CD20 in plasma samples as a potential contributing mechanism to relapsed or refractory cases of NHL. Although the prevalence appears to be low, this is consistent with previous reports and supports investigation of the clinical utility, including utility as a potential predictive biomarker, of sequencing this gene during treatment with CD20xCD3 BsTCE. Future and ongoing work will screen additional cohorts and therapy combinations.
