Lisa O'flynn PhD

Dr. OFlynn is a Director of Process Development at Avectas Ltd. She Investigates cell-based therapies for application in organ transplantation have grown significantly. Her PhD work described the ex vivo generation of donor bone marrow-derived dendritic cells (BMDCs) and examined the therapeutic potential of genetic and pharmaceutical modifications of BMDCs for application in allogeneic transplantation. The treatment of BMDC with dexamethasone (Dexa) to induce an immature, maturation-resistant phenotype was comprehensively examined in this study. BMDC and Dexa BMDC phenotype, antigen-presenting cell function, and their immunomodulatory properties were examined and fully characterized.

Moreover, in a fully MHC I/II mismatched rat corneal transplantation model injection of the donor (DA) derived BMDC or Dexa BMDCs significantly prolonged corneal allograft survival without the need for additional immunosuppression. With both cell therapies, she observed a significant reduction in the level of allograft cellular infiltration, a significant increase in the ratio of intragraft FoxP3 expressing regulatory cells, and evidence of a donor-specific alloantibody response. Taken together, this comprehensive study demonstrates detailed analysis of the significant therapeutic effect of donor-derived BMDCs with and without glucocorticoid treatment in corneal allograft survival by modulation of the alloimmune response at the level of both the allograft and the draining lymph nodes. This body of research represents a novel therapeutic approach for the prevention of corneal allograft rejection.