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Medicine

Dr Sean Hua Lim MBChB, MRCP, PhD, FRCPath

Associate Professor and Honorary Consultant in Haematological Oncology

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Sean Lim is an Associate Professor and Honorary Consultant in Haematological Oncology. Her position is funded by a Cancer Research UK Advanced Clinician Scientist Fellowship. This enables her to uniquely bridge the divide between laboratory and clinic. Her research interest is in cancer immunotherapy.

As a clinician scientist, my aim is to translate and accelerate discoveries from the laboratory into meaningful differences in patient care. My research examines how we can exploit our own immune system to destroy cancer using antibodies.

Sean completed her medical degree at the University of Bristol in 2001, and then trained in general medicine before specialising in Haematology, which she completed in 2012. During this time, she was awarded a clinical research training fellowship by the Medical Research Council which enabled her to simultaneously complete a PhD in cancer immunotherapy at Southampton in 2011. Her work was awarded the Royal College of Pathologists’ Specialty Research Medal (2012) and UK CLL Forum’s Catovsky Prize (2011).

Through a Cancer Research UK Clinician Scientist Fellowship award, Dr Lim spent two years as a visiting postdoctoral research fellow in Professor Ron Levy’s laboratory at Stanford University, USA. In 2015, she returned to Southampton to lead her own research group. Her recent work was awarded the British Association for Cancer Research (BACR) Roger Griffin Prize for Cancer Drug Discovery. She is also a practicing clinician subspecialising in lymphoma.

Qualifications

Appointments Held

Research interests

Sean Lim’s primary research interest is in understanding and developing new immunotherapeutic approaches in cancer. Her work is primarily concentrated on B-cell lymphoma, a common cancer in adulthood. Lymphoma is a highly treatable cancer, but in some patients the disease follows a relapsing-remitting course. For decades, it was conventionally treated with chemotherapy and radiotherapy but advances on these approaches had plateaud and any improvement in response rates was offset by treatment toxicity. In the 1990s, rituximab, a monoclonal antibody targeting CD20, a marker expressed on B cells entered clinical use. It was the first drug to successfully increase the cure rates for this condition since the introduction of chemotherapy and radiotherapy. More significantly, rituximab provided a proof-of-principle that the immune system can be manipulated by a simple antibody, to fight cancer. Dr Lim’s research is now focused on how we can further exploit our immune system to fight cancer through the use of monoclonal antibodies. 

Previous research

Dr Lim’s initial research focused on understanding why rituximab failed in a proportion of cases. Her work showed that rituximab not only binds to its target CD20, but also to another marker present on B cells, Fc gamma RIIb (CD32b). Malignant B cells express more CD32b than normal B cells, and CD32b promotes the internalisation of rituximab into B cell. Consequently, this reduces engagement of immune cells, which kill rituximab-coated B cells, and hence, resistance to rituximab. Thus the efficacy of rituximab could be improved by blocking its interaction with CD32b. Her preclinical findings led to the development of a first-in-man, Phase I clinical trial of a novel CD32b antibody in lymphoma for which she is a sub-investigator in.

Present research

Her current research examines how the adaptive immune system can be exploited to enhance the efficacy of direct, tumour-targeting antibodies like rituximab. She has shown T-cell stimulation with an agonistic antibody (e.g. against CD27) causes the release of cytokines and chemokines which activate and promote the infiltration of macrophages to the tumour site. These macrophages are then able to phagocytose more tumour cells if they have been opsonised by a tumour-targeting antibody. These preclinical data have also led to the development of a multicentre CRUK-sponsored Phase II study of rituximab and varlilumab in relapsed/refractory B-cell lymphoma, for which Dr Lim is also the Chief Investigator. Dr Lim hopes to validate these findings in patients, and also understand whether these results can be extended to cancers beyond rituximab and lymphoma.

Other projects actively running in the lab include:

  1. An antibody drug discovery project for peripheral T cell lymphomas
  2. Cancer antigen discovery in colorectal cancer
  3. Development of novel antagonistic antibodies

Funding: Cancer Research UK, CONACYT, Ervaxx, Bioinvent, Celldex Therapeutics, Horizon 2020.

Tumour cell is coated by a tumour-targeting antibody
Tumour cell is coated by a tumour-targeting antibody

Department(s)

Cancer Sciences

Supervision

My research team comprises two research technicians (Mrs Anna Turaj and TBC), two PhD students (Ms Franziska Heckel and Ms Sonia Murillo Barrera) and a postdoctoral fellow (Dr Michael Marshall).

Internal responsibilities

  • Centre for Cancer Immunology Steering Committee
  • Antibody & Vaccine Group Executive Committee
  • Faculty Enterprise Board

External responsibilities (past and present)

  • MRC Infection and Immunity Board member
  • NCRI Science Lymphoma Subgroup member
  • CRUK Pioneer Award member
  • NCRI Cancer Conference Treatment subcommittee
  • Irish HRB grants' committees
  • Clinical expert in NICE Single Technology Appraisal Evidence Review Group
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Articles

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Review

Integrated PhD project supervisor and BMEDSc project marker and supervisor

Dr Sean Hua Lim
Antibody & Vaccine Group
Centre for Cancer Immunology
University Hospital Southampton (MP127)
Tremona Road, Southampton SO16 6YD

Email: s.h.lim@soton.ac.uk

Room Number: SGH/3007/MP127

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