A high affinity recombinant antibody to the human EphA3 receptor with enhanced ADCC activity

Abstract

EphA3is expressed in solid tumors and leukemias and is an attractive target for the therapy. We have generated a panel of Humaneered® antibodies to the ligand-binding domain using a Fab epitope-focused library that has the same specificity as monoclonal antibody mIIIA4. A high-affinity antibody was selected that competes with the mIIIA4 antibody for binding to EphA3 and has an improved affinity of ～1?nM. In order to generate an antibody with potent cell-killing activity the variable regions were assembled with human IgG1k constant regions and expressed in a Chinese hamster ovary (CHO) cell line deficient in fucosyl transferase. Non-fucosylated antibodies have been reported to have enhanced binding affinity for the IgG receptor CD16a (FcγRIIIa). The affinity of the antibody for recombinant CD16a was enhanced approximately 10-fold. This resulted in enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity against EphA3-expressing leukemic cells, providing a potent antibody for the evaluation as a therapeutic agent.     

Epstein–Barr virus patterns in US Burkitt lymphoma tumors from the SEER residual tissue repository during 1979–2009

Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein–Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. BL tissues from residual tissue repositories, and two academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV‐encoded RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi‐squared statistics, and Student's t‐test. Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0–19, 20–34, 35–59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age group 0–19 to 55% in age group 20–34, and fell to 25% in age group 60+ years, p = 0.08); with race (56% in Blacks/Hispanics vs 21% in Whites/Asians/Pacific Islanders, p = 0.006); and by HIV status (64% in HIV positive vs 22% in HIV negative cases, p = 0.03). EBER positivity was demonstrated in about one‐third of tumors and it was strongly associated with race and HIV status, and marginally with age‐group.     

COVID-19 Pandemic: The Role of EMS Physicians in a Community Response Effort

Abstract

The COVID-19 pandemic is a worldwide historical event that will continue to affect nearly every aspect of ordinary life, including affecting our economic, political, and healthcare eco-systems. An effective pandemic response demands a coordinated and integrated response across community healthcare stakeholders, including Public Health and Emergency Management Officials. EMS systems are in a unique position and perform an essential role on the frontlines of COVID-19, including facilitating coordination of response efforts to COVID-19 within their communities while supporting public health mitigation efforts to slow the spread of the SARS-CoV-2. EMS physicians serve their communities at a unique intersection as clinical leaders, population health experts, and advocates. This paper examines and recommends crucial roles for EMS physician leaders as communities work together in pandemic response.