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Prof Persis Amrolia
Molecular Immunology Unit, UCL Institute of Child Health
30 Guilford Street
London
WC1N 1EH
Appointment
  • Professor of Transplantation Immunology
  • ICH - Molecular Immunology Unit
  • Dept of Infection & Immunity
  • Faculty of Population 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 Royal College of Pathologists, UK
2006 FRCP Fellow of the Royal College of Physicians Royal College of Physicians
1999 MRCPath Member of the Royal College of Pathologists Royal College of Pathologists, UK
1996 PhD Doctor of Philosophy University of London
1992 MRCP Member of the Royal College of Physicians Royal College of Physicians
1989 MBBS Bachelor of Medicine/Bachelor of Surgery University of London
1986 BSc Bachelor of Science University of London
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