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Group

Genomics-Guided Cancer Immunotherapy Group

Unit(s) of assessment: Allied Health Professions, Dentistry, Nursing and Pharmacy

Research theme: Health and Wellbeing

School: School of Science and Technology

Overview

Sergio Rutella is a licensed haematologist and Professor of Cancer Immunotherapy at the John van Geest Cancer Research Centre. His academic career has been predicated on the bench-to-bedside-to-bench paradigm in Haematology. Over the last 25 years, Professor Rutella has been engaged in clinical and translational research focusing on immunotherapy approaches to improve the outcome of haematological malignancies, with an emphasis on antibody-based therapeutics and haematopoietic stem cell transplantation. He has an extensive track record of leading studies that involve a strong correlative component and collaborating with other investigators, both basic and clinical. At Nottingham Trent University, Professor Rutella’s research program focuses on visualising the state of cancer-immune interactions in individual patients and on biomarker discovery, with the aim to implement the design of rational immunotherapy approaches, to guide treatment choices and to minimise toxicity.

During his academic career, Professor Rutella has authored and co-authored 216 full-length, peer-reviewed publications (H-index=55; i10-index=166; times cited=10,520) and 13 book chapters and has secured £4,606,278 of research funding as principal investigator/co-investigator. His teaching contributions are made to UG and PG projects on the BIOL40111 MSc Research Project module, the BIOL40102 "Research Methods and Bioethics" module, and the BIOL33171 "Immunology and Virology" module.

Dr Jayakumar Vadakekolathu is a Research Fellow in the John van Geest Cancer Research Centre. His research mainly focused on integrating various post-genomics analytical methods for understanding molecular and cellular cross-talk between stromal, tumour, and immune components of solid and hematologic malignancies. He is also focused on studying molecular mediators which create a permissive microenvironment for tumour immune evasion and metastasis progression using high-throughput transcriptomics and proteomics platforms at NTU.

Dr Vadakekolathu obtained an MSc (Biotechnology) from Bharathidasan University, Tiruchirappalli, TN, India, and an MRes In Advanced Genomics and Proteomics Sciences (AGPS) which was jointly provided by The University of Nottingham and Nottingham Trent University. He completed his PhD in Cancer Immunology at Nottingham Trent University (NTU) under the direction of Professor Robert C Rees, Dr Stéphanie McArdle, and Dr David Boocock in 2013. For the last 6 years, he has been working as a post-doctoral Research Fellow at John van Geest Cancer Research Centre, Nottingham. Since 2017, his work has mainly focused on understanding the TME of Acute Myeloid Leukemia (AML) led by Professor Sergio Rutella.

Areas of clinical research interest for Professor Rutella’s team include:

- Novel immunotherapy approaches for haematological malignancies

- Does the Immune System Matter in Treatment for AML?

-  IFN-gamma-mediated tumour immune evasion and response to immunotherapy

-  Analysis of high-dimensional transcriptomic data from human tumours

-  Pharmacological re-activation of mutant TP53 in acute myeloid leukaemia and its effect on the expression of inflammatory mediators

Collaboration

John F. DiPersio, MD PhD, Professor and Director, Centre for Gene and Cellular Immunotherapy (CGCI), Washington University School of Medicine, St. Louis, MO, USA

Leo Luznik, MD, Professor of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA

Jan K. Davidson-Moncada, MD PhD, Director of Clinical Development and Research, MacroGenics Inc., Rockville, MD, USA

Sarah K. Tasian, MD, Assistant Professor of Pediatrics and PI – Leukaemia Biorepository, Division of Oncology, Children’s Hospital of Philadelphia, PA, USA

Marc Schmitz, MD, Professor of Immunology and Head of NCT/UCC Immune Monitoring Unit, Institut für Immunologie, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

Martin Bornhäuser, MD, Professor of Haematology/Oncology, Co-Head of Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

Publications

Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia. Uy GL, Aldoss I, Foster MC, Sayre PH, Wieduwilt MJ, Advani AS, Godwin JE, Arellano ML, Sweet KL, Emadi A, Ravandi F, Erba HP, Byrne M, Michaelis LC, Topp MS, Vey N, Ciceri F, Carrabba MG, Paolini S, Huls GA, Jongen-Lavrencic M, Wermke M, Chevallier P, Gyan E, Recher C, Stiff PJ, Pettit KM, Löwenberg B, Church SE, Anderson E, Vadakekolathu J, Santaguida MT, Rettig MP, Muth J, Curtis T, Fehr E, Guo K, Zhao J, Bakkacha O, Jacobs K, Tran K, Kaminker P, Kostova M, Bonvini E, Walter RB, Davidson-Moncada JK, Rutella S, DiPersio JF. (2020). Blood Sep 14: blood.2020007732. DOI: 10.1182/blood.2020007732.

TP53 abnormalities correlate with immune infiltration and associate with response to flotetuzumab immunotherapy in acute myeloid leukemia. *Lai C, *Vadakekolathu J (*=equal contributors), Reeder S, Church SE, Hood T, Lourdusamy A, Rettig MP, Aldoss I, Advani AS, Godwin J, Wieduwilt MJ, Arellano M, Muth J, Yau TO, Ravandi F, Sweet K, Altmann H, Foulds GA, Stölzel F, Middeke JM, Ciciarello M, Curti A, Valk PJM, Löwenberg B, Gojo I, Bornhäuser M, DiPersio JF, Davidson-Moncada JK, Rutella S. . Blood Advances (In press).

Immune landscapes predict therapeutic resistance, immunotherapy response and clinical outcomes in acute myeloid leukemia. Vadakekolathu J, Minden MD, Hood T, Church SE, Reeder S, Altmann H, Sullivan A, Viboch E, Patel T, Ibrahimova N, Warren SE, Arruda A, Liang Y, Smith TH, Foulds GA, Bailey MD, Gowen-MacDonald J, Muth J, Schmitz M, Cesano A, Pockley AG, Valk PJM, Löwenberg B, Bornhäuser M, Tasian SK, Rettig MP, Davidson-Moncada JL, DiPersio JF, Rutella S.(2020). Science Translational Medicine 12 (Issue 546): eaaz0463. DOI: 10.1126/scitranslmed.aaz0463

The Society for Immunotherapy of Cancer biomarkers resource document: clinical biomarkers and data sharing Volume I - Conceptual challenges. Rutella S, Cannarile MA, Gnjatic S, Gomes B, Guinney J, Karanikas V, Karkada M, Kirkwood JM, Kotlan B, Masucci GV, Meeusen E, Monette A, Naing A, Thorsson V, Tschernia N, Wang E, Wells D, Wyant TL, Cesano A. Journal for Immunotherapy of Cancer (In press).

The Society for Immunotherapy in Cancer biomarkers resource document: clinical biomarkers and data sharing Volume II - Practical challenges. Cesano A, Cannarile MA, Gnjatic S, Gomes B, Guinney J, Karanikas V, Karkada M, Kirkwood JM, Kotlan B, Masucci GV, Meeusen E, Monette A, Naing A, Thorsson V, Tschernia N, Wang E, Wells D, Wyant TL, Rutella S.. Journal for Immunotherapy of Cancer (In press).

A parsimonious 3-gene signature predicts clinical outcomes in an acute myeloid leukemia multicohort study. Wagner S, Vadakekolathu J, Tasian SK, Altmann H, Bornhauser M, Pockley AG, Ball GR, Rutella S. (2019). Blood Adv. 3(8): 1330-1346.

MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer. Vadakekolathu J, Al-Juboori SIK, Johnson C, Schneider A, Buczek ME, Di Biase A, Pockley AG, Ball GR, Powe DG, Regad T. (2018). Cell Death Dis. 9(3):344.

Related projects

Recent projects:

Creative Thinking to Cure Cancer: Targeting aggressive cancer using immune-based therapies

Personalised Immunotherapy Approaches for Acute Leukaemia

Recent research funding:

Investigating the cellular content of HSCT donor/graft and patient samples using immune cell profiling, Anthony Nolan Research Institute, London, UK (2020-2021), £22,000 (Co-Lead: Dr Diana Hernandez).

Identification of prognostic/predictive immune gene signatures in patients with relapsed/refractory acute myeloid leukaemia receiving flotetuzumab immunotherapy. MacroGenics, Inc., Rockville, United States of America and NanoString Technologies, Inc., Seattle, United States of America

Identification of prognostic/predictive immune gene signatures in patients with advanced gastric cancer receiving immunotherapy with pembrolizumab and anti-HER2 antibodies. MacroGenics, Inc., Rockville, United States of America and NanoString Technologies, Inc., Seattle, United States of America

Tipifarnib and interferon signalling in acute myeloid leukaemia. Kura Oncology, San Diego, United States of America

Immunological profiling of acute myeloid leukaemia, Roger Counter Foundation, Dorset, UK (2016-2019), £116,000

PhD Programme (2017-2020): "Implementation of a novel immune gene profiling platform for the generation and analysis of high-dimensional transcriptomic data from human tumours" (co- funded by NanoString Technologies Inc., USA).

Microenvironmental targets for restoring anti-tumour immunity in childhood acute leukaemia, Qatar National Research Fund (2016-2020), NPRP8-2297-3-494; $800,160

Related news stories:

MacroGenics Announces Publication of Flotetuzumab Interim Phase 1/2 Clinical Trial Results in Blood

Gene Expression Signature May Predict Chemo Resistance, Immunotherapy Response in AML Patients

Study paves way for faster, more accurate therapies for hard-to-treat leukaemia patients

MacroGenics Announces Publication in Science Translational Medicine Supporting Flotetuzumab Pivotal Study in Patients with Refractory Acute Myeloid Leukemia

Patients with altered TP53 R/R AML have increased tumor immune-infiltration and show sensitivity to flotetuzumab

AACR20 Day 1 Highlights: Breast Cancer, Lung Cancer, and the Microbiome

Will TP53-mutated AML respond to immunotherapy?

MacroGenics Presents Margetuximab Data in Gastroesophageal Cancer at the ESMO 2019 Congress