Transplantation Immunology Research Group

Group Leader: Dr Ronjon Chakraverty

Introduction

The Transplantation Immunology Group is based at the Hampstead Campus and forms part of a large Immunotherapy Programme at UCL. Our research involves both pre-clinical, translational and phase I/II projects that aim to develop innovative strategies to improve the anti-tumour effects of blood and bone marrow transplantation. We work closely with the groups of Professor Hans Stauss/Dr. Emma Morris (Tumour Immunology, Cellular and Gene Therapy), and Dr. Clare Bennett (Dendritic Cell Immunotherapy), with a number of fellows or PhD students working on joint projects.

Research

Following blood or bone marrow transplantation, donor T cells that have been infused as part of the graft or given at a later time point, become activated in response to antigenic differences between the donor and the recipient. This effect can be co-opted to generate anti-tumour activity, an effect termed the ‘graft-versus-tumour’ (GVT) response. Alternatively, donor T cells may react against normal tissues, leading to graft-versus-host disease (GVHD). See figure below: 

These outcomes depend upon how donor T cells recognize antigen and this, in turn is influenced by nature of the cells presenting antigen. We are interested in how distinct non-haematopoietic and haematopoietic cell populations in the recipient influence the development of donor T cell immunity after transplantation. This research offers the opportunity to develop new approaches to manipulating antigen presentation for therapeutic benefit e.g. following vaccination.

Ultimately, durable anti-tumour immunity requires that T cells with anti-tumour reactivity engraft and then persist long-term in the recipient. By exploring clinically relevant models, we are examining the mechanisms that influence the long-term survival of anti-tumour T cells such that they can provide long-term immune surveillance. An improved understanding of the pathways that regulate this property of ‘memory’ is helping us to engineer T cells that can maintain their functions over long periods.

Current Research Projects

Pre-clinical:

• The role of antigen presentation by the innate immune system in GVHD
• The influence of co-inhibitory and co-stimulatory signalling in GVHD and GVL
• The effect of antigen presentation by non-haematopoietic cells upon anti-tumour immunity
• Tolerance pathways in dendritic cells
• In vivo selection of anti-tumour T cells
• Tumour targeting of anti-tumour cells
• Memory programming of therapeutic T cells

Translational:

• Selection of human memory T cells for clinical application

Phase I/II clinical studies:

• ProT4; multi-centre randomised phase II study to evaluate the efficacy of prophylactic transfer of CD4 lymphocytes after T-cell depleted reduced intensity HLA-identical sibling transplantation for indolent non-Hodgkin’s lymphoma and CLL