Leading organizational transformation: an action research study

Purpose – This study addresses a specific gap in the literature that centers on individual perspective of leadership within the context of organizational transformation. It explores synergies between leadership, analyzed as a combination of individual and plural perspectives, and managerial drivers relating to organizational transformation (communicating, mobilizing, and evaluating), with a focus on capturing the essence of the context. Design/methodology/approach – The study examines a complex organizational transformation initiative faced by an Italian, family-owned fashion design company through an action research project. Findings – The results illustrate that context may play a role in accelerating the implementation of plural forms of leadership and their effectiveness during some phases of transformation. Specific emerging manifestations of leadership and synergies with transformation drivers are identified. Research limitations/implications – This is a single case study derived from an action research project. Although the approach is congruent with the nature of the phenomenon and the purpose of the study, it does not aim for generalizability, and as such further empirical investigation is advocated. Originality/value – The article offers an original perspective on leadership of organizational transformation, discussing in particular the co-existence of individual and plural leadership and the role of context

Soluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies

Background On the basis of efficacy in mouse tumor models, multiple CD137 (4-1BB) agonist agents are being preclinically and clinically developed. The costimulatory molecule CD137 is inducibly expressed as a transmembrane or as a soluble protein (sCD137). Moreover, the CD137 cytoplasmic signaling domain is a key part in approved chimeric antigen receptors (CARs). Reliable pharmacodynamic biomarkers for CD137 ligation and costimulation of T cells will facilitate clinical development of CD137 agonists in the clinic. Methods We used human and mouse CD8 T cells undergoing activation to measure CD137 transcription and protein expression levels determining both the membrane-bound and soluble forms. In tumor-bearing mice plasma sCD137 concentrations were monitored on treatment with agonist anti-CD137 monoclonal antibodies (mAbs). Human CD137 knock-in mice were treated with clinical-grade agonist anti-human CD137 mAb (Urelumab). Sequential plasma samples were collected from the first patients intratumorally treated with Urelumab in the INTRUST clinical trial. Anti-mesothelin CD137-encompassing CAR-transduced T cells were stimulated with mesothelin coated microbeads. sCD137 was measured by sandwich ELISA and Luminex. Flow cytometry was used to monitor CD137 surface expression. Results CD137 costimulation upregulates transcription and protein expression of CD137 itself including sCD137 in human and mouse CD8 T cells. Immunotherapy with anti-CD137 agonist mAb resulted in increased plasma sCD137 in mice bearing syngeneic tumors. sCD137 induction is also observed in human CD137 knock-in mice treated with Urelumab and in mice transiently humanized with T cells undergoing CD137 costimulation inside subcutaneously implanted Matrigel plugs. The CD137 signaling domain-containing CAR T cells readily released sCD137 and acquired CD137 surface expression on antigen recognition. Patients treated intratumorally with low dose Urelumab showed increased plasma concentrations of sCD137. Conclusion sCD137 in plasma and CD137 surface expression can be used as quantitative parameters dynamically reflecting therapeutic costimulatory activity elicited by agonist CD137-targeted agents