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Adoptive chimeric antigen receptor (CAR)-engineered natural killer (NK) cells have shown promise in treating various cancers. However, limited immunological memory and access to sufficient numbers of allogenic donor cells have hindered their broader preclinical and clinical applications. Here, we first assess eight different CAR constructs that use an anti-PD-L1 nanobody and/or universal anti-fluorescein (FITC) single-chain variable fragment (scFv) to enhance antigen-specific proliferation and anti-tumor cytotoxicity of NK-92 cells against heterogenous solid tumors. We next genetically engineer human pluripotent stem cells (hPSCs) with optimized CARs and differentiate them into functional dual CAR-NK cells. The tumor microenvironment responsive anti-PD-L1 CAR effectively promoted hPSC-NK cell proliferation and cytotoxicity through antigen-dependent activation of phosphorylated STAT3 (pSTAT3) and pSTAT5 signaling pathways via an intracellular truncated IL-2 receptor β-chain (ΔIL-2Rβ) and STAT3-binding tyrosine-X-X-glutamine (YXXQ) motif. Anti-tumor activities of PD-L1-induced memory-like hPSC-NK cells were further boosted by administering a FITC-folate bi-specific adapter that bridges between a programmable anti-FITC CAR and folate receptor alpha-expressing breast tumor cells. Collectively, our hPSC CAR-NK engineering platform is modular and could constitute a realistic strategy to manufacture off-the-shelf CAR-NK cells with immunological memory-like phenotype for targeted immunotherapy. 

There is growing evidence that emphasizing the social and personal contexts of engineering can open up the field to people who have been conspicuously underrepresented, particularly women and girls. Recent research and advances in educational policy have advocated for reframing engineering education to prioritize social responsibility, empathy, and care for others as integral aspects of engineering practice. But how do we measure things like empathy in engineering practices of younger children? This paper features work from a three-year design-based research project in which we used narrative elements to frame engineering problems in ways that evoked empathy for others’ needs, and examined the intersections between expressions of empathy and engineering design practices among girls ages 7-14. This paper outlines the theoretical underpinnings of this approach, and our methods for observing empathy and engineering practices in this age group. 

Reframing engineering activities to emphasize the needs of others has the potential to strengthen engineering practices like problem scoping, while also providing more inclusive and socially relevant entry points into engineering problems. In this design-based research project, we developed novel strategies for adding narratives to engineering activities to deepen girls’ engagement in engineering practices by evoking empathy for the users of their designs. We describe a set of hands-on engineering activities developed through iterative development and testing with 190 girls (ages 7-14) at the New York Hall of Science. Findings show how elements of narrative (like characters and settings) evoked learners’ empathy, and how learners’ expressions of empathy related to practices like problem scoping and iteration. A set of design principles summarizes critical features of the narrative activities for evoking empathy and supporting the engineering design process. Finally, we offer recommendations for practitioners who would like to use narratives to engage learners in approaching engineering problems from a user-centered perspective. This work has implications for the development of inclusive and engaging engineering activities that appeal to elementary and middle school learners in a wide range of settings.