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Immune checkpoint therapy has resulted in remarkable improvements in the outcome for certain cancers. To broaden the clinical impact of checkpoint targeting, we devised a strategy that couples targeting of the cytokine-inducible SH2-containing (CIS) protein, a key negative regulator of interleukin (IL)-15 signaling, with fourth generation 'armored' chimeric antigen receptor (CAR-IL-15) engineering of cord blood (CB) derived natural killer (NK) cells. This combined strategy boosted NK cell effector function through enhancing the Akt/mTORC1 axis and c-MYC signaling, resulting in increased aerobic glycolysis. When tested in a lymphoma mouse model, this combined approach improved NK cell anti-tumor activity more than either alteration alone, eradicating lymphoma xenografts without signs of any measurable toxicity. We conclude that targeting a cytokine checkpoint further enhances the antitumor activity of IL-15 secreting armored CAR-NK cells by promoting their metabolic fitness and anti-tumor activity. This combined approach represents a promising milestone in the development of the next generation of NK cells for cancer immunotherapy.

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This paper reflects upon the technology acceptance model (TAM) from the perspective of the post positivistic philosophy of science. I explore what it is to know, what a theory is, and what it means to be scientific in the context of TAM. In particular, I review criteria for determining whether TAM is scientific or not in light of post-positivistic debates about the nature of science. For this purpose, I apply Popper's principle of demarcation, which determines whether a theory-like TAM-is falsifiable and the logical connection argument to show that connections between actions and intentions cannot be subjected to empirical testing similar to connections between chemical entities. I also draw on Kuhn's notion of scientific revolutions to observe the degree to which TAM has become normal science. Finally, I review TAM from the Lakatosian perspective of scientific research programs to evaluate whether the program is advancing or declining. My main objective is not to provide a conclusive evaluation of TAM as a research program or a paradigm, but to open the philosophical foundations of TAM for scrutiny so that it can be evaluated not only within the validation rules followed by its proponents, but by applying a set of well known criteria established in the post-positivistic views of science.

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The study of the role of power in managing information systems (IS) still offers a major epistemological challenge to researchers in the field. Although significant work has been done, there is yet to emerge a research approach that permits a penetrating study of the phenomenon of power by virtue of adopting a Machiavellian stance. This paper proposes such an approach in the form of an interpretivist position combined with a theoretical framework whose origin lies in political science and the sociology of technology. In developing its philosophical argument, the paper compares three meta-theories that have been applied to study IS: Phenomenology, Critical Theory and Structuration Theory. All three are compared in terms of their epistemological position regarding the relationship between power and IS. We argue that, although enlightening, those metatheories fail to unravel the hidden and strategic nature of power. The paper concludes by proposing a particular theoretical formulation that, rather than censoring power and politics, will provide the epistemological means for unravelling them.