Karadimitris Lab

Contact

Anastasios Karadimitris PhD, MRCP, FRCPath

  • Professor of Haematology and Consultant Haematologist
  • Director of Centre

+44 (0)20 3313 4017
a.karadimitris@imperial.ac.uk

Areas of research

Regulatory genomics of multiple myeloma

Primary and secondary genetic events underpin the transcriptional changes that drive myeloma oncogenic transcriptional programmes. These are executed by deregulated transcription factors and chromatin binding proteins. Our aim is to understand the role of known and novel transcription factors/chromatin modifiers in the biology of multiple myeloma and discover and validate therapeutic targets.

Our experimental tools include -omics assays (ChIP-seq, ATAC-seq, RNA-seq, Capture-C), chromatin proteomics, gene editing approaches including CRISPRi and relevant in vitro and in vivo models of multiple myeloma.

Immunotherapy of multiple myeloma

The Karadimitris group have been studying the biology and therapeutic potential of invariant NKT cells (iNKT) in acute graft-versus-host disease (aGVHD) and blood cancers. They showed that donor iNKT cells protect recipients of allogeneic stem cell transplant from aGVHD and iNKT cell equipped with chimaeric antigen receptor against CD19 (CAR19-iNKT) outperform CAR19-T cells in pre-clinical models of B cell lymphoma. Following this lead, the group is now developing CAR-iNKT cell-based immunotherapy against MM that includes development and validation of CAR against established and novel targets.

Our experimental tools include short- and long term in vitro assays (including longitudinal Incucyte live-cell imaging) and xenograft animal models of blood cancers and myeloma.

In parallel to pre-clinical studies, the group are pursuing clinical development of the CAR-iNKT cell platform for blood cancers.

Citation

BibTex format

@article{Rotolo:2016:10.1111/bjh.13976,
author = {Rotolo, A and Caputo, V and Karadimitris, A},
doi = {10.1111/bjh.13976},
journal = {British Journal of Haematology},
pages = {350--364},
title = {The prospects and promise of chimeric antigen receptor immunotherapy in multiple myeloma},
url = {http://dx.doi.org/10.1111/bjh.13976},
volume = {173},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Despite encouraging therapeutic advances, multiple myeloma (MM) remains an incurable malignancy. The exciting results of chimaeric antigen receptor (CAR)-based immunotherapy in CD19+ B-cell malignancies have spurred a great interest in extending the use of the CAR technology to other cancers, including MM.Availability of a specific, tumour-restricted antigen is crucial for the design of successful antibody-based CAR therapy. However, in MM, as in other malignancies, the relative dearth of such antigens-targets represents the main obstacle for the wider pre-clinical development and clinical application of the CAR technology.Here we provide an overview of the current progress and future promises of CAR technology in MM therapy. We highlight that, owing to its complexity, phenotypic and functional heterogeneity and the impact of the microenvironment, MM poses several challenges for CAR-based therapeutic approaches. Nevertheless, for the same reasons, MM can serve as a paradigm for better understanding, optimization and overall improvement of the CAR technology for the benefit of cancer and myeloma patients.
AU  - Rotolo,A
AU  - Caputo,V
AU  - Karadimitris,A
DO  - 10.1111/bjh.13976
EP  - 364
PY  - 2016///
SN  - 1365-2141
SP  - 350
TI  - The prospects and promise of chimeric antigen receptor immunotherapy in multiple myeloma
T2  - British Journal of Haematology
UR  - http://dx.doi.org/10.1111/bjh.13976
VL  - 173
ER  -
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