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Prof Persis Amrolia
Molecular Immunology Unit, UCL Institute of Child Health
30 Guilford Street
  • Professor of Transplantation Immunology
  • ICH Infect, Imm, Infla. & Physio Med
  • Institute of Child Health
  • Faculty of Pop Health Sciences
Research Summary
1. Adoptive Immunotherapy with Allodepleted Donor T-cells We have demonstrated that it is possible to specifically delete the alloreactive donor T-cells responsible for GVHD by stimulating them with HLA-mismatched host antigen presenting cells, followed by allodepletion with an immunotoxin recognising activated (CD25+ve) alloreactive cells. We showed that anti-viral responses against CMV, EBV and adenovirus, as assessed using IFN-? ELISPOT and tetramer assays, were preserved following allodepletion with anti-CD25 immunotoxin and that T-cell responses to the myeloid tumour antigen proteinase 3 were also retained using this approach. Based on these studies, in collaboration with Baylor College of Medicine, we performed a Phase 1 clinical study of addback of allodepleted donor T-cells after haplo-identical stem cell transplant, comparing immune reconstitution after immunotherapy with 2 different doses of allodepleted T-cells. I was responsible for the design and execution of this protocol. 16 patients were treated and we showed that patients receiving 105 cells/kg/dose showed significantly accelerated T-cell recovery, improved T-cell repertoire and earlier anti-viral responses to CMV and EBV, with a very low incidence of GVHD. These data demonstrate that allodepleted donor T-cells can be safely used to improve T-cell recovery after haplo-identical SCT and may broaden the applicability of this approach. We are currently refining this approach so that higher doses of T-cells can be infused without causing GVHD. We have shown that a subset of proliferating (CFSE-dim) alloreactive T-cells do not express CD25 and that these can be efficiently targeted using negative immunomagnetic selection with anti-CD71. Our data suggest that combined CD25/71 depletion enhances the degree of depletion of alloreactive T-cells compared with CD25-based strategies and we are now scaling-up our method with a view to a further clinical study of adoptive immunotherapy.
Teaching Summary
I participate in regular local teaching programmes for: ? Paediatric SHOs, Haematology and Immunology registrars and nurses at Great Ormond Street Hospital. ? MSc. course in Immunology, Institute of Child Health ? Annual teaching course for Haematology SpRs at UCH. Additionally at a national level I teach regularly on: ? UK Paediatric Oncology Training (POTG) course for Paediatric Haematology/Oncology SpRs. ? UK BMT Nursing course of South Bank University. ? Royal College of Paediatrics and Child Health Immunology Training course for Immunology and Infectious Disease SpRs.
Academic Background
2007 FRCPath Fellow of the Royal College of Pathologists – Haematology Royal College of Pathologists, UK
2006 FRCP Fellow of the Royal College of Physicians – Medicine Royal College of Physicians
1999 MRCPath Member of the Royal College of Pathologists – Haematology Royal College of Pathologists, UK
1996 PhD Doctor of Philosophy – Medicine University of London
1992 MRCP Member of the Royal College of Physicians – Medicine Royal College of Physicians
1989 MBBS Bachelor of Medicine/Bachelor of Surgery – Medicine/Surgery University of London
1986 BSc Bachelor of Science – Biochemistry University of London
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