Leukotriene B4: A potential mediator and biomarker for cardiac allograft vasculopathy.

Background: Cardiac allograft vasculopathy (CAV) remains the leading cause of long-term graft failure and mortality after heart transplantation. Effective preventive and treatment options are not available to date, largely because underlying mechanisms remain poorly understood. We studied the potential role of leukotriene B4 (LTB4), an inflammatory lipid mediator, in the development of CAV.

Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate.

Allogeneic transplantation of pancreatic islets for patients with difficult-to-control diabetes mellitus is severely hampered by the requirement for continuous immunosuppression and its associated morbidity. We report that allogeneic transplantation of genetically engineered (B2M, CIITA, CD47), primary, hypoimmune, pseudo-islets (p-islets) results in their engraftment into a fully immunocompetent, diabetic non-human primate wherein they provide stable endocrine function and enable insulin independence without inducing any detectable immune response in the absence of immunosuppression. Hypoimmune primary p-islets may provide a curative cell therapy for type 1 diabetes mellitus.

Synthetic immune checkpoint engagers protect HLA-deficient iPSCs and derivatives from innate immune cell cytotoxicity.

Immune rejection of allogeneic cell therapeutics remains a major problem for immuno-oncology and regenerative medicine. Allogeneic cell products so far have inferior persistence and efficacy when compared with autologous alternatives. Engineering of hypoimmune cells may greatly improve their therapeutic benefit.

Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques.

Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient's immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing of off-the-shelf cell products. Previously, we generated mouse and human hypoimmune pluripotent (HIP) stem cells by depleting HLA class I and II molecules and overexpressing CD47 (B2MCIITACD47). To determine whether this strategy is successful in non-human primates, we engineered rhesus macaque HIP cells and transplanted them intramuscularly into four allogeneic rhesus macaques.