Targeting HER2/neu with a fully human IgE to harness the allergic reaction against cancer cells

Breast and ovarian cancer are two of the leading causes of cancer deaths among women in the United States. Overexpression of the HER2/neu oncoprotein has been reported in patients affected with breast and ovarian cancers, and is associated with poor prognosis. To develop a novel targeted therapy for HER2/neu expressing tumors, we have constructed a fully human IgE with the variable regions of the scFv C6MH3-B1 specific for HER2/neu. This antibody was expressed in murine myeloma cells and was properly assembled and secreted. The Fc region of this antibody triggers in vitro degranulation of rat basophilic cells expressing human FcεRI (RBL SX-38) in the presence of murine mammary carcinoma cells that express human HER2/neu (D2F2/E2), but not the shed (soluble) antigen (ECDHER2) alone. This IgE is also capable of inducing passive cutaneous anaphylaxis in a human FcεRIα transgenic mouse model, in the presence of a cross-linking antibody, but not in the presence of soluble ECDHER2. Additionally, IgE enhances antigen presentation in human dendritic cells and facilitates cross-priming, suggesting that the antibody is able to stimulate a secondary T-cell anti-tumor response. Furthermore, we show that this IgE significantly prolongs survival of human FcεRIα transgenic mice bearing D2F2/E2 tumors. We also report that the anti-HER2/neu IgE is well tolerated in a preliminary study conducted in Macaca fascicularis (cynomolgus) monkeys. In summary, our results suggest that this IgE should be further explored as a potential therapeutic against HER2/neu overexpressing tumors, such as breast and ovarian cancers.Fil: Daniels, Tracy R.. University of California at Los Angeles; Estados UnidosFil: Leuchter, Richard K.. University of California at Los Angeles; Estados UnidosFil: Quintero, Rafaela. University of California; Estados UnidosFil: Helguera, Gustavo Fernando. University of California at Los Angeles; Estados Unidos. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodríguez, José A.. University of California at Los Angeles; Estados UnidosFil: Martínez Maza, Otoniel. University of California at Los Angeles; Estados UnidosFil: Schultes, Birgit C.. Advanced Immune Therapeutics, Inc.; Estados Unidos. Momenta Pharmaceuticals, Inc.; Estados UnidosFil: Nicodemus, Christopher F.. Advanced Immune Therapeutics, Inc.; Estados UnidosFil: Penichet, Manuel L.. University of California at Los Angeles; Estados Unido

Transforming libraries into learning collaborative hubs: the current state of physical spaces and the perceptions of Greek librarians concerning implementation of the “Learning Commons” model

Purpose: With the technological innovation dominating higher education, the university libraries, as physical spaces, continue to play a crucial role in connecting students with knowledge. The emergence of the “Learning Commons” serves as a catalyst in the design of library spaces, renewing libraries’ roles and missions and making them popular to Millennials for new reasons. This study aims to record Greek librarians' views on the current situation in Greek academic libraries regarding physical space design, services provided and the existence of the “Learning Commons” model characteristics. Design/methodology/approach: This study was conducted through an online survey structured questionnaire (closed-ended, five-point Likert scale, multiple-choice and statements questions). This study population comprised librarians working in 37 academic institutions and colleges. The collected data were subjected to descriptive statistical analysis. The research questions were answered using variables creation and the tests, t-test, ANOVA and Kruskal–Wallis. The groups of questions were tested for their reliability using the Cronbach's alpha coefficient. Findings: In total, 186 librarians responded to this study. The responses revealed that participants were willing and ready to accept and support a different approach to academic library physical spaces use, according to the shared learning spaces model. However, this requires changes in the organization's vision, further growth and evolution. Although recently most Greek academic libraries have made significant progress in developing their services to function as information and digital hubs, they do not function as learning collaborative hubs, since the “Learning Commons” model is not reflected in their buildings. Originality/value: The creation of new academic libraries according to the “common” model is a rapidly evolving issue that affects Greek libraries. This paper highlights the characteristics of libraries that should be adopted in the modern era, the new roles of academic librarians and the importance of an appropriate design of the physical space to achieve optimal learning outcomes. At the same time, this paper is one of the few that illustrates librarians', and not users', perceptions of these changes. This paper is a good research example, and the methodology for measuring this type of context could be used by other future research approaches in other countries. © 2022, Emerald Publishing Limited