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UCL Great Ormond Street Institute of Child Health

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Prof Persis Amrolia

Professor of Transplantation Immunology

ICH Infect, Imm, Infla. & Physio Med

UCL GOS Institute of Child Health

Joined UCL
1st Oct 2007

Research summary

1. Chimeric Antigen Receptor (CAR) T-cells for the treatment of paediatric acute lymphoblastic leukaemia (ALL)

International research leader in this approach, where T-cells genetically redirected to kill leukaemia.  I led 1st EU study of this straegy in paediatric ALL, with collaborators from UCL developed a novel 2nd generation CAR and have implemented a multi-centre UK study (CARPALL) with this with national referrals.  This has enabled UK patients to have access to this ground-breaking new treatment. Early results show unprecedented complete response rates in otherwise incurable patients. To prevent relapse, I am collaborating with Autolus to set up the first study of bispecific CD19+CD22 CART cells worldwide.  This may transform management of relapsed ALL by avoiding need for Bone Marrow Transplant (BMT).

2. Allodepleted donor T-cells (ADTs) to improve immunity after BMT.

My group has a long-term programme of research on allodepletion as a strategy to improve immune responses to viral infections SCT.  In this approach, we adoptively transfer T-cells from the donor after SCT, having specifically removed those that would attack the patient, causing graft-versus-host disease (GVHD).  I am Chief Investigator of MRC funded, multi-centre, Phase II randomised clinical study (ICAT) to determine if ADTs can safely improve immunity after unrelated donor BMT.  This approach may reduce morbidity/mortality from viral infections after BMT.

3. Genetically modified T cells to treat Lymphoproliferative Disease (LPD) after solid organ transplant.

LPD is a major complication of organ transplant and arises when T cell immunity to EBV is suppressed by drugs used to prevent rejection.  We have genetically engineered EBV-specific T cells so they can work despite immunosuppression.  In collaboration with Bluebirdbio, we are testing this approach in a clinical study (start Q4 2017).  If successfull, this will benefit organ transplant patients by avoiding the toxicity of chemotherapy and reducing risk of graft rejection.

4. Antibody-based conditioning for BMT

BMT requires intensive chemotherapy to enable engraftment of donor stem cellsl (HSC). Based on our previous landmark clinical study (Straathof Lancet 2006), we continue to work on developing lytic antibodies (MAbs) directed against c-kit to enable HSC engraftment without chemotherapy.  Since these MAbs are haematopoietic-specific, they should not cause toxicity to other tissues resulting in reduced toxicity.  Have developed anti-kit MAbs and now collaborating with industry partners to enhance lytic activity.  Plan to test in clinical studies whether such reagents can enable engraftment of donor HSC. This could potentially revolutionise BMT and gene therapy by avoiding need for chemotherapy.

Teaching summary

Education

Royal College of Pathologists, UK
FRCPath, Haematology | 2007
Royal College of Physicians
FRCP, Medicine | 2006
Royal College of Pathologists, UK
MRCPath, Haematology | 1999
University of London
PhD, Medicine | 1996
Royal College of Physicians
MRCP, Medicine | 1992
University of London
MBBS, Medicine/Surgery | 1989
University of London
BSc, Biochemistry | 1986
Publications