Diminished immune cell adhesion in hypoimmune ICAM-1 knockout human pluripotent stem cells.

Gene edited human pluripotent stem cells are a promising platform for developing reparative cellular therapies that evade immune rejection. Existing first-generation hypoimmune strategies have used CRISPR/Cas9 editing to modulate genes associated with adaptive immune responses, but have largely not addressed the innate immune cells, such as neutrophils, that mediate inflammation and rejection processes occurring early after graft transplantation. We identify the adhesion molecule ICAM-1 as a hypoimmune target that plays multiple critical roles in both adaptive and innate immune responses post-transplantation.

Development of Potent and Selective RIPK1 Degraders Targeting Its Nonenzymatic Function for Cancer Treatment.

Receptor-interacting protein kinase 1 (RIPK1) is a threonine/serine kinase that serves as a critical regulator of immune responses and cell death pathways, functioning through both its kinase activity and nonenzymatic scaffolding function. The scaffolding function of RIPK1 contributes to both intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs), making it a compelling therapeutic target for cancer treatment. Recent studies have highlighted RIPK1's potential as a key modulator for improving the efficacy of immune-stimulatory therapies, such as ICBs and X-ray radiotherapy (XRT).

Diminished Immune Cell Adhesion in Hypoimmune ICAM-1 Knockout Pluripotent Stem Cells.

Hypoimmune gene edited human pluripotent stem cells (hPSCs) are a promising platform for developing reparative cellular therapies that evade immune rejection. Existing first-generation hypoimmune strategies have used CRISPR/Cas9 editing to modulate genes associated with adaptive (e.g.

Generation of the NeoThy mouse model for human immune system studies.

Humanized mouse models, created via transplantation of human hematopoietic tissues into immune-deficient mice, support a number of research applications, including transplantation immunology, virology and oncology studies. As an alternative to the bone marrow, liver, thymus humanized mouse, which uses fetal tissues for generating a chimeric human immune system, the NeoThy humanized mouse uses nonfetal tissue sources. Specifically, the NeoThy model incorporates hematopoietic stem and progenitor cells from umbilical cord blood (UCB) as well as thymus tissue that is typically discarded as medical waste during neonatal cardiac surgeries.