Key research focuses include:
- Novel target development
- Application of Synthetic biology approaches to T-cell engineering
- Refining CAR T-cell strategies to reduce toxicity and prevent antigen negative escape
- Modulating the interaction of the tumour microenvironment with CAR T-cells
- Semi-automated CAR T-cell manufacturing
- Allogeneic CAR T-cell approaches.
Chimeric Antigen Receptors (CARs)
Chimeric Antigen Receptors (CARs) are artificial T-cell receptors. CARs are typically generated by fusing the antigen binding portion of a monoclonal antibody to intracellular T-cell signaling domains (see figure). Genetically engineering T-cells to express a CAR allows the generation of T-cells with any desired specificity.
CAR T-cell therapeutics targeting CD19 in refractory B-cell malignancies have resulted in sustained responses in a significant proportion of patients. CD19 CAR T-cell therapy is the most important advance in the field of malignancy haematology in a generation.
CAR T therapy in 60 seconds
Dr Claire Roddie, Associate Professor at UCL and Consultant Haematologist at UCLH, explains CAR T cell therapy in just 60 seconds.
The CAR T programme in detail
The UCL CAR T-cell programme
The UCL CAR T-cell programme is centered at the UCL Cancer Institute where researchers focus on developing CAR T-cell therapies for adult cancers.
CAR T-cell studies at UCL derived from UCL technology
The UCL Campus (inc. UCLH and GOSH) has Europe's largest CAR T-cell programme. There are 10 studies using technology at UCL. Many of these are academic, but several are funded by industrial partners.
CAR T GMP manufacturing team
Our programme encompasses a broad-ranging portfolio of studies actively recruiting patients with B and T cell malignancies, myeloma, and neuroblastoma. We have several new trials in the pipeline.
Cell and Vector Manufacturing Core
Cell and Vector Manufacturing
Based at the Royal Free Hospital in Hampstead, we translate novel gene engineered and genome edited cellular therapies. The team excels in process development and GMP manufacturing for Phase I studies
Key publications
- Roddie C, Dias J, O'Reilly MA ... Pule MA, Peggs KS. Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2021 Oct 20;39(30): 3352-3363.
- Wawrzyniecka PA, Ibrahim L, Gritti G, Pule MA, Maciocia PM. Chimeric antigen receptor T cells for gamma-delta T cell malignancies. Leukemia. 2022 Feb;36(2):577-579.
- Biasco L, Izotova N, Rivat C ... Pule M, Thrasher AJ, Amrolia PJ. Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients. Nat Cancer. 2021 Jun;2(6): 629-642.
- Agliardi G, Liuzzi AR, Hotblack A ... Pule MA, Tugues S, Straathof K, Becher B. Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma. Nat Commun. 2021 Jan 19;12(1): 444.
- Straathof K, Flutter B, Wallace R ... Pule M, Anderson J. Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma. Sci Transl Med. 2020 Nov 25;12(571): eabd6169.
- EGhorashian S, Kramer AM, Onuoha S ... Pule MA, Amrolia PJ. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med. 2019 Sep;25(9): 1408-1414.
- Stavrou M, Philip B, Traynor-White C ... Pule M. A Rapamycin-Activated Caspase 9-Based Suicide Gene. Mol Ther. 2018 May 2;26(5): 1266-1276.
- Lee L, Draper B, Chaplin N ... Yong K, Pule M. An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Blood. 2018 Feb 15;131(7): 746-758.
- Maciocia PM, Wawrzyniecka PA, Philip B ... Pule MA. Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nat Med. 2017 Dec;23(12): 1416-1423.
- Qasim W, Zhan H, Samarasinghe S ... Pule M, Veys P. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med. 2017 Jan 25;9(374):eaaj2013. Erratum in: Sci Transl Med. 2017 Feb 15;9(377): aam9292.
- Mock U, Nickolay L, Philip B ... Pule M, Thrasher AJ, Qasim W. Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS prodigy. Cytotherapy. 2016 Aug;18(8): 1002-1011.
- Poirot L, Philip B, Schiffer-Mannioui C ... Peggs K, Pule M, Scharenberg AM, Smith J. Multiplex Genome-Edited T-cell Manufacturing Platform for "Off-the-Shelf" Adoptive T-cell Immunotherapies. Cancer Res. 2015 Sep 15;75(18): 3853-64.
- Philip B, Kokalaki E, Mekkaoui L ... Peggs KS, Pule M. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood. 2014 Aug 21;124(8): 1277-87.
- Rossig C, Pule M, Altvater B, et al. Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia. Leukemia. 2017 May;31(5): 1087-1095.
- Menger L, Sledzinska A, Bergerhoff K ... Pule M, Hererro J, Peggs KS, Quezada SA. TALEN-Mediated Inactivation of PD-1 in Tumor-Reactive Lymphocytes Promotes Intratumoral T-cell Persistence and Rejection of Established Tumors. Cancer Res. 2016 Apr 15;76(8):2087-93. Erratum in: Cancer Res. 2016 Oct 15;76(20):6130; Cancer Res. 2017 Jun 15;77(12):3379.
News and features
UCL spinout Autolus gains US approval for cancer therapy
Autolus Therapeutics, a UCL spinout, has received authorisation from the UK Medicines and Healthcare products Regulatory Agency (MHRA) for a next-generation CAR T-cell therapy.
New CAR-T cell therapy gives hope for patients with aggressive blood cancer
A new chimeric antigen receptor T cell (CAR-T) therapy has delivered promising results in patients with an aggressive blood cancer, in results from a clinical trial led by researchers at UCL and UCLH.
Cancer therapy with potential to transform lupus treatment delivered in UK first
The first UK patients have received an innovative immunotherapy to treat the most serious form of lupus, as part of a clinical trial led by UCL and UCLH.
New immunotherapy shows promise against rare childhood cancer
A novel CAR T-cell therapy developed by researchers at UCL and designed to target cancerous tumours, has shown promising early results in children with neuroblastoma, a rare form of childhood cancer.
26 November 2020
War in the Blood wins Best Science Documentary prize
The BBC 2 documentary 'War in the Blood' highlighting the UCL CAR T programme led by Dr Martin Pule has won the Sargent-Disc Best Science Documentary in the annual Grierson Awards.
13 November 2020
'War in the Blood', a film about treating cancer patients with CAR T cell therapy
A new BBC film looks at the work of scientists at UCL and clinicians at UCLH working together on groundbreaking ‘first in-human’ immunotherapy trials.
2 July 2019
Young Blood: meet the Irish doctors with a new weapon against cancer
Two committed Irish doctors are pioneering a groundbreaking new cancer treatment. Martin Pule and Claire Roddie tell Independent.IE about the perks and pain of the world of clinical trials.
New CAR T-cell therapy for leukaemia associated with fewer harmful side effects
A novel CAR T-cell therapy developed by UCL researchers has shown very promising results for children with previously incurable acute lymphoblastic leukaemia (ALL).
Breakthrough Cell Therapies Treating Blood Cancers
Early results from the COBALT trial and other UCL / UCLH studies show that aggressive cancers can be tamed with CAR-T therapies. Karl Peggs explains more about advances in cell therapy treatments.
UCL 2nd in the world and top in Europe for CAR T research activity
UCL ranks second in the world and top in Europe for the number of inventions and patent applications made in relation to the revolutionary new cancer treatment CAR T-cell therapy – key markers of CAR T research activity at UCL and UCLH.
1 May 2019
Animated film on CAR T-cell therapy launched for GCSE students
The UCLH Biomedical Research Centre (BRC) has today launched an animated film for GCSE and A level students on CAR T-cell therapy – a revolutionary approach to the treatment of cancer.
11 April 2019
