No abstract

Anti-CD2 treatment provides targeted immunomodulatory properties that have demonstrated clinical usefulness to condition the immune system and to treat transplant rejection. The treatment is species-specific due to structural CD2 antigen differences between nonhuman primates and humans. Herein, we report the safety profile and efficacy of two modifications of the same anti-CD2 monoclonal antibody in cynomolgus macaques. Twelve subjects received one i.v. anti-CD2 (of rat or rhesus type) dose each, range 1-4 mg/kg, and were followed for 1-7 days. Treatment effects were evaluated with flow cytometry on peripheral blood and histopathological evaluation of secondary lymphoid organs. In vitro inhibitory activity on primary MHC disparate mixed lymphocyte reactions (MLRs) was determined. Upon anti-CD2 treatment, CD4 + , CD8 + memory subsets were substantially depleted. Na€ ıve T cells and Tregs were relatively spared and exhibited lower CD2 expression than memory T cells. Early immune reconstitution was noted for na€ ıve cells, while memory counts had not recovered after one week. Both antibodies displayed a concentration-dependent MLR inhibition. Lymph node examination revealed no significant lymphocyte depletion. None of the animals experienced any significant study drug-related adverse events. This study outlines the safety and pharmacodynamic profile of primate-specific anti-CD2 treatment, relevant for translation of anti-CD2-based animal models into clinical trials. Transplant International 2020; 33: 98-107

No abstract

Thoracic duct (TD) injuries can carry significant morbidity and mortality to patients. When medical and percutaneous interventions are unsuccessful at cure, open surgical ligation is often necessary but limited by poor visualization of the TD and all the morbidities associated with thoracotomy. We describe here a video-assisted thoracoscopic surgery (VATS) approach to TD ligation that offers the benefits of minimally invasive surgery in addition to improved visualization to optimize success rates. Operative Techniques in Thoracic and Cardiovasculary Surgery 21:152-159

Purpose of review: To review the recent progress in xenotransplantation achieved through genetic engineering and discuss the potential of tolerance induction to overcome remaining barriers to extended xenograft survival. Recent findings: The success of life-saving allotransplantation has created a demand for organ transplantation that cannot be met by the supply of human organs. Xenotransplantation is one possible solution that would allow for a nearly unlimited supply of organs. Recent genetic engineering of swine has decreased the reactivity of preformed antibodies to some, but not all, potential human recipients. Experiments using genetically-modified swine organs have now resulted in survival of life-supporting kidneys for over a year. However, the grafts show evidence of antibody-mediated rejection on histology, suggesting additional measures will be required for further extension of graft survival. Tolerance induction through mixed chimerism or thymic transplantation across xenogeneic barriers would we well-suited for patients with a positive crossmatch to genetically-modified swine or relatively negative crossmatches to geneticallymodified swine, respectively. Summary: This review highlights the current understanding of the immunologic processes in xenotransplantation, and describes the development and application of strategies designed to overcome them from the genetic modification of the source animal to the induction of tolerance to xenografts.