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- ORCID ID = 0000-0002-8347-9867
- Website = https://www.ucl.ac.uk/cancer/research/ucl-car-t-programme
- GMC = #6113780
Degrees/professional Qualifications with subjects and dates (Maximum 1,000 characters)
- 2008 Certificate of Specialist Training in Haematology, RCPI
- 2007 Fellow Royal College of Pathologists (FRCPath)
- 1999 US Medical Licensing Examinations Completed 0-518-972-5
- 1997 Member Royal College of Physicians in Ireland (MRCP)
- 1995 Medicine – University College Dublin, MB Bch BAO (Honors)
Present and Previous Positions with dates (Maximum 1,000 characters)
Jan 2011 – Current Senior Lecturer in Haematology University College London
Director - UCL Cancer Institute Chimeric Antigen Receptor Programme
Jan 2015 – Current Chief Scientific Officer, Autolus Ltd
Jan 2007 – Dec 2010 MRC Clinician Scientist Fellow University College London
June 2005 – December 2006 Clinical Lecturer in Haematology University College London
August 2001- May 2005 Traveling Fulbright Scholar and Research Fellow
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston
July 1998 – June 2001 Haematology Specialist Training, Dublin
Awards and invited talks:
UCL Business award 2015 for the founding of Autolus Ltd
BBSRC Innovator of the year 2016, Most promising Innovator
Since 2015 I have given >50 invited talks including at ASGCT, Cellicon Valley, EHA and Keystone.
Relevant Current and Recent Research Grants:
I have only listed grants I am PI of or else very substantial awards:
Moulton Fund: multi-edited CD30 CAR T-cell therapy for r/r Hodgkins Lymphoma. Principle Investigator 2020-2024. Value £1.4M
Moulton Fund: EGFRvIII CAR T-cell therapy for glioblastoma Multiforme. Co-Investigator. 2020-2024. Value £1.3M
MRC Project grant “CD21 CAR T-cell therapy for T-ALL”. Principle investigator 2019-2022. Value £680k.
MRC DPFS grant “A protein-based method for allogeneic CAR T-cell therapy”. Principle investigator 2019-2024. Value £2.2M
Wellcome Trust. Health Innovation Fund. £2.7M. CAR T-cell therapy of CNS Lymphoma. Principle Investigators. Starting Sept 2016, 4 years.
EU 20/20 scheme. CARAT consortium. Partner. EURO 1M. Next generation CAR T-cell engineering. Started Sept 2016. 5 years.
NIHR i4i. Phase I/II study of CAR19 in relapsed/refractory ALL. Principle Investigator. £3.9M. 3.5 years starting Sept. 2015
Innovate UK / BBSRC Consortium. Coordinator. “Large-scale production of lentiviral vectors” £1.8M. 3 years starting Aug 2015
CRUK Project grant “EGFRvIII targeting of glioma by CAR T-cells”. £180,000 over 3 years starting Sept. 2015.
CRUK Project grant “Targeting CD160 for immunotherapy of chronic lymphocytic leukaemia”. Pule[PI], £160,000 over 2 years.
EU FP7 ATECT “Advanced T-cell Engineering” I am coordinator. EU 6 million; 3 million to UCL.
Patents Filed/commercialization
I have filed > 50 patents. In 2020, a review of the CAR T patent landscape, Nature Biotechnology listed me as the #2 global inventor in CAR T (Lyu et al). In 2021, a review by the EPO listed me as the #1 inventor of CAR T cell patents at the EPO. Patents I have filed teach amongst many inventions new suicide genes (WO2013153391 and WO2017137759). new receptor types (WO2015052536, WO2016139487), a strategy to target T cell Lymphomas (WO2015132598) and ways of CAR targeting multiple antigens simultaneously (WO2016174407).
Designs in first in Man studies
I have designed numerous T cell engineering components which have been tested in human subjects
Component | Description | Study / papers |
14g2a-CD28-OX-Z | 3rd generation CAR recognizing GD2 | Baylor College of Medicine |
Fmc63-CH1CH2-Z | First generation CAR recognizing CD19 | UCL/Munster (EU funded) |
huK666-CD28-Z | 2nd generation humanized CAR recognizing GD2 | CRUK funded study NCT02761915 |
RQR8/4G7-41BB-Z | Bicistronic suicide gene + 2nd generation CD19 CAR designed for allo use | Cellectis / Allogene / UCL NCT02746952 and |
CnBx21 | Calcineurin mutant renders T cells resistant to Tacrolimus | Bluebird Bio funded at UCL NCT03131934 |
CAT-41BB-Z | Fast off-rate CD19 CAR designed to improve engraftment and reduce tox | Multiple UCL / Autolus NCT02935257 and NCT04404660 |
APRIL-HNG-CD28OXZ | Third generation BCMA/TACI CAR | |
AUTO3 Cassette | First bi-cistronic CD19/CD22 co-targeting cassette | Autolus NCT03289455 and NCT03287817 |
AUTO 4 Cassette | Suicide gene / TRBC1 targeting CAR | Autolus NCT03590574 |
CAT/9A8 41BB-Z | Double transduction CD19 fast-off rate CAR with high-sensitivity CD22 CAR |
Book Chapters - William’s Haematology (10th edition) – Chapter on CAR T cells.
Public engagement
I collaborated with the animator Greg Foot to create a Ted Ed video “How to bio hack your T cells to fight cancer”. This is available on youtube and has been watched >500,000 times.
I collaborated with BBC2 to create a documentary detailing CAR T first in man clinical study. This won the 2020 Grierson Award. It is available on BBC iPlayer, and on the director’s page on Vimeo.
Engagement with Industry and Entrepreneurship
In 2007, I established a collaboration with the genome editing company Cellectis. With their CSO, Andy Scharenberg, we conceived the idea of TAL mediated TCR and CD52 ko, allowing the use of Campath to prevent CAR T rejection. The first-in-man test was at UCL (PMID: 28123068). The cassette I developed for this (RQR8/4G7-41BB-Z) is currently in study by Cellectis in B-ALL (NCT02808442), and in DLBCL by Allogene (NCT03939026).
In 2015, I founded Autolus Ltd a CAR T cell company based in London. Autolus has since floated on the Nasdaq, raised >$500M and currently employs over 300 people and opened 5 clinical studies. Autolus has licensed CAT19-41BB-z, the fast off-rate CD19 CAR I developed at UCL and this is now in a phase Ib/II registration study (NCT04404660).
I am on the scientific advisory board of Mana Therapeutics, a company developing neo TIL therapy for acute myeloid leukemia. I am also on the scientific advisory board of Virocell Therapeutics.
Selected Publications
Citations – 10905; h-index – 44; [pubmed link]; Orcid id – 0000-0002-8347-9867
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.
Roddie C, Dias J, O'Reilly MA, Abbasian M, Cadinanos-Garai A, Vispute K, Bosshard-Carter L, Mitsikakou M, Mehra V, Roddy H, Hartley JA, Spanswick V, Lowe H, Popova B, Clifton-Hadley L, Wheeler G, Olejnik J, Bloor A, Irvine D, Wood L, Marzolini MAV, Domning S, Farzaneh F, Lowdell MW, Linch DC, Pule MA, Peggs KS. J Clin Oncol. 2021 Aug 31:JCO2100917. doi: 10.1200/JCO.21.00917. Online ahead of print. PMID: 34464155
Chimeric antigen receptor T cells for gamma-delta T cell malignancies.
Wawrzyniecka PA, Ibrahim L, Gritti G, Pule MA, Maciocia PM. Leukemia. 2021 Aug 13. doi: 10.1038/s41375-021-01385-0. Online ahead of print. PMID: 34389804
Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients.
Biasco L, Izotova N, Rivat C, Ghorashian S, Richardson R, Guvenel A, Hough R, Wynn R, Popova B, Lopes A, Pule M, Thrasher AJ, Amrolia PJ. Nat Cancer. 2021 Jun;2(6):629-642. doi: 10.1038/s43018-021-00207-7. Epub 2021 May 24. PMID: 34345830
Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma
Agliardi G, Anna Rita Liuzzi AR, Hotblack A, De Feo D, Núñez N, Stowe CL, Friebel E, Nannini F, Rindlisbacher L, Roberts TA, Ramasawmy R, Williams IP, Siow BM, Lythgoe MF, Kalber TL, Quezada SA, Pule MA, Tugues S, Straathof K, Becher B. Nat Commun. 2021 Jan 19;12(1):444. doi: 10.1038/s41467-020-20599-x.
Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma. Straathof K, Flutter B, Wallace R, Jain N, Loka N, Depani S, Wright G, Thomas S, Weng-Kit Cheung G, Gileadi T, Stafford S, Kokalaki E, Barton J, Marriott C, Rampling D, Ogunbiyi O, Akarca AU, Marafioti R, Inglott S, Gilmour K, Al-Hajj M, Day W, McHugh K, Biassoni L, Sizer N, Barton C, Edwards D, Dragoni I, Silvester J, Dyer K, Traub S, Elson L ,Brook S, Westwood N, Robson L, Bedi A, Howe K, Barry A, Duncan C, Barone G, Pule M, Anderson J. Sci Transl Med 2020 Nov 25;12(571):eabd6169. doi: 10.1126/scitranslmed.abd6169.
Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Ghorashian A, Kramer AM, Onuoha A, Wright G, Bartram J, Richardson R, Albon S, Casanovas-Company J, Castro F, Popova B, Villanueva K, Yeung J, Vetharoy W, Guvenel A, Wawrzyniecka PA, Mekkaoui L, Weng-Kit Cheung G, Pinner D, Chu J, Lucchini G, Silva J, Ciocarlie O, Lazareva A, Inglott S, Gilmour KC, Ahsan G, Ferrari M, Manzoor S, Champion K, Brooks T, Lopes A, Hackshaw A, Farzaneh F, Chiesa R, Rao K, Bonney D, Samarasinghe S, Goulden N, Vora A, Veys P, Hough R, Wynn R, Pule MA, Amrolia PJ. Nat Med 2019 Sep;25(9):1408-1414. doi: 10.1038/s41591-019-0549-5.
A Rapamycin-Activated Caspase 9-Based Suicide Gene. Stavrou M, Philip B, Traynor-White C, Davis CG, Onuoha S, Cordoba S, Thomas S, Pule M. Mol Ther. 2018 May 2;26(5):1266-1276. doi: 10.1016/j.ymthe.2018.03.001.
An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Lee L, Draper B, Chaplin N, Philip B, Chin M, Galas-Filipowicz D, Onuoha S, Thomas S, Baldan V, Bughda R, Maciocia P, Kokalaki E, Neves MP, Patel D, Rodriguez-Justo M, Francis J, Yong K, Pule M. Blood. 2018 Feb 15;131(7):746-758. doi: 10.1182/blood-2017-05-781351. Epub 2017 Dec 28.
Targeting the T cell receptor β-chain constant region for immunotherapy of T-cell malignancies. Maciocia PM, Wawrzyniecka PA, Philip B, Ricciardelli I, Akarca AU, Onuoha SC, Legut M, Cole DK, Sewell AK, Gritti G, Somja J, Piris MA, Peggs KS, Linch DC, Marafioti T, Pule MA. Nat Med. 2017 Dec;23(12):1416-1423. doi: 10.1038/nm.4444. Epub 2017 Nov 13.
Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Qasim W, Zhan H, Samarasinghe S, Adams S, Amrolia P, Stafford S, Butler K, Rivat C, Wright G, Somana K, Ghorashian S, Pinner D, Ahsan G, Gilmour K, Lucchini G, Inglott S, Mifsud W, Chiesa R, Peggs KS, Chan L, Farzeneh F, Thrasher AJ, Vora A, Pule M, Veys P. Sci Transl Med. 2017 Jan 25;9(374):eaaj2013. doi: 10.1126/scitranslmed.aaj2013.
Automated manufacturing of chimeric antigen receptor T-cells for adoptive immunotherapy using CliniMACS prodigy. Mock U, Nickolay L, Philip B, Cheung GW, Zhan H, Johnston IC, Kaiser AD, Peggs K, Pule M, Thrasher AJ, Qasim W. Cytotherapy. 2016 Aug;18(8):1002-11. doi: 10.1016/j.jcyt.2016.05.009.
Multiplex Genome-Edited T-cell Manufacturing Platform for "Off-the-Shelf" Adoptive T-cell Immunotherapies. Poirot L, Philip B, Schiffer-Mannioui C, Le Clerre D, Chion-Sotinel I, Derniame S, Potrel P, Bas C, Lemaire L, Galetto R, Lebuhotel C, Eyquem J, Cheung GW, Duclert A, Gouble A, Arnould S, Peggs K, Pule M, Scharenberg AM, Smith J. Cancer Res. 2015 Sep 15;75(18):3853-64. doi: 10.1158/0008-5472.CAN-14-3321. Epub 2015 Jul 16.
A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K, Flutter B, Marin V, Marafioti T, Chakraverty R, Linch D, Quezada SA, Peggs KS, Pule M. Blood. 2014 Aug 21;124(8):1277-87. doi: 10.1182/blood-2014-01-545020. Epub 2014 Jun 26.
Vaccination to improve the persistence of CD19CAR gene-modified T-cells in relapsed pediatric acute lymphoblastic leukemia. Rossig C, Pule M, Altvater B, Saiagh S, Wright G, Ghorashian S, Clifton-Hadley L, Champion K, Sattar Z, Popova B, Hackshaw A, Smith P, Roberts T, Biagi E, Dreno B, Rousseau R, Kailayangiri S, Ahlmann M, Hough R, Kremens B, Sauer MG, Veys P, Goulden N, Cummins M, Amrolia PJ. Leukemia. 2017 May;31(5):1087-1095. doi: 10.1038/leu.2017.39. Epub 2017 Jan 27.
TALEN-Mediated Inactivation of PD-1 in Tumor-Reactive Lymphocytes Promotes Intratumoral T-cell Persistence and Rejection of Established Tumors. Menger L, Sledzinska A, Bergerhoff K, Vargas FA, Smith J, Poirot L, Pule M, Hererro J, Peggs KS, Quezada SA. Cancer Res. 2016 Apr 15;76(8):2087-93. doi: 10.1158/0008-5472.CAN-15-3352.