Patient Demographics and Clinical Outcomes Among Type 1 Diabetes Patients Using Continuous Glucose Monitors: Data From T1D Exchange Real-World Observational Study.

BACKGROUND: The benefits of Continuous Glucose Monitoring (CGM) on glycemic management have been demonstrated in numerous studies; however, widespread uptake remians limited. The aim of this study was to provide real-world evidence of patient attributes and clinical outcomes associated with CGM use across clinics in the U.S. based T1D Exchange Quality Improvement (T1DX-QI) Collaborative. METHOD: We examined electronic Health Record data from eight endocrinology clinics participating in the T1DX-QI Collaborative during the years 2017-2019. RESULTS: Among 11,469 type 1 diabetes patients, 48% were CGM users. CGM use varied by race/ethnicity with Non-Hispanic Whites having higher rates of CGM use (50%) compared to Non-Hispanic Blacks (18%) or Hispanics (38%). Patients with private insurance were more likely to use CGM (57.2%) than those with public insurance (33.3%) including Medicaid or Medicare. CGM users had lower median HbA1c (7.7%) compared to nonusers (8.4%). Rates of diabetic ketoacidosis (DKA) and severe hypoglycemia were significantly higher in nonusers compared to CGM users. CONCLUSION: In this real-world study of patients in the T1DX-QI Collaborative, CGM users had better glycemic control and lower rates of DKA and severe hypoglycemia (SH) events, compared to nonusers; however, there were significant sociodemographic disparities in CGM use. Quality improvement and advocacy measures to promote widespread and equitable CGM uptake have the potential to improve clinical outcomes.

A Costimulatory CAR Improves TCR-based Cancer Immunotherapy.

T-cell receptors (TCR) recognize intracellular and extracellular cancer antigens, allowing T cells to target many tumor antigens. To sustain proliferation and persistence, T cells require not only signaling through the TCR (signal 1), but also costimulatory (signal 2) and cytokine (signal 3) signaling. Because most cancer cells lack costimulatory molecules, TCR engagement at the tumor site results in incomplete T-cell activation and transient antitumor effects. To overcome this lack of signal 2, we genetically modified tumor-specific T cells with a costimulatory chimeric antigen receptor (CoCAR). Like classical CARs, CoCARs combine the antigen-binding domain of an antibody with costimulatory endodomains to trigger T-cell proliferation, but CoCARs lack the cytotoxic CD3ζ chain to avoid toxicity to normal tissues. We first tested a CD19-targeting CoCAR in combination with an HLA-A*02:01-restricted, survivin-specific transgenic TCR (sTCR) in serial cocultures with leukemia cells coexpressing the cognate peptide-HLA complex (signal 1) and CD19 (signal 2). The CoCAR enabled sTCR+ T cells to kill tumors over a median of four additional tumor challenges. CoCAR activity depended on CD19 but was maintained in tumors with heterogeneous CD19 expression. In a murine tumor model, sTCR+CoCAR+ T cells improved tumor control and prolonged survival compared with sTCR+ T cells. We further evaluated the CoCAR in Epstein-Barr virus-specific T cells (EBVST). CoCAR-expressing EBVSTs expanded more rapidly than nontransduced EBVSTs and delayed tumor progression in an EBV+ murine lymphoma model. Overall, we demonstrated that the CoCAR can increase the activity of T cells expressing both native and transgenic TCRs and enhance antitumor responses.