NexTGen
Develop novel therapies to target unique features in solid tumours in children


Professor Catherine Bollard, Co-team Lead
Professor of Pediatrics and Microbiology, Immunology and Tropical Medicine
NexTGen

Dr Martin Pule Co-Team Lead
Clinical Senior Lecturer
NexTGen
INSTITUTIONS
8
LOCATIONS
UK, US, France
FUNDED BY
Cancer Research UK, National Cancer Institute, The Mark Foundation for Cancer Research
SPECIALISMS
oncology, immunology, glycobiology, proteomics, mathematics
Next-generation cell therapies for children with solid cancers
Funded by:

By building a deep understanding of the development of solid cancers in children, applying advanced cellular engineering technologies and performing progressive clinical studies, the NexTGen team seeks to produce effective CAR T-cell therapies for children with sarcomas and brain tumours.
Cancer is a leading cause of death by disease in children worldwide. Although survival has increased for some paediatric cancers, such as blood cancers, survival for some solid tumours has seen little improvement for more than 30 years. Standard treatments can cause severe long-term health complications, such as learning difficulties, abnormal growth and infertility. For children who relapse, few second-line treatments are typically available.
Many barriers exist to developing specific, effective treatments for children with solid tumours – for example, because adult cancers are very different to childhood ones, therapies that are developed to exploit cancer’s vulnerabilities in adults have limited efficacy in children.
The Cancer Grand Challenges NexTGen team aims to overcome these barriers and deepen our understanding of childhood solid cancers, to discover new targets and develop and optimise novel CAR T-cell therapies for children with these diseases. The discoveries may improve survival in children with solid cancers and diminish the lifelong toxicities often experienced by survivors.
Tackling the Solid Tumours in Children Challenge
Five interlinked aims are central to the team’s effort:
- Surface targets
Cancer vulnerabilities differ between childhood and adult tumours and novel targets for cell therapy in children are urgently needed. To engineer T-cells that can recognise cancer cells, the team will explore a range of surface antigens, including traditional surface proteins, aberrant glycosylation and the “dark antigens” expressed from regions of the genome that are usually silenced.
- The environment
A major barrier to T-cell therapy is the tumour microenvironment, a complex multicellular milieu that can enable tumours to resist treatment. The team aims to design genetically encodable components that either render therapeutic T-cells resistant to the microenvironment or modulate the microenvironment to make tumours more vulnerable.
- Component engineering
Here, the team hopes to develop novel receptors that precisely target the antigens identified in aim 1, to increase cell therapies’ potency and ability to resist inhibition by the tumour microenvironment. The most promising components will be evaluated preclinically and then in early-phase clinical trials.
- Preclinical models
Most existing models of paediatric cancer do not incorporate the immune environment, making it challenging to test cell therapies. To test their cell therapies and decide which should proceed to clinical testing, the team will optimise novel modelling methods, including tumour-on-a-chip, patient-derived immune xenografts and mathematical models of cells’ dynamics and interactions with the microenvironment.
- Clinical testing
Early in the programme, the team will implement three innovative phase I clinical trials testing different steps in the development of T cells: a highly customisable CAR region; an engineering component that blocks a treatment-inhibiting cytokine in the microenvironment; two T-cell platforms for engineering and two administration routes. Synergy between the clinical studies and the team’s basic and preclinical research will support iterative refinement of the CAR T-cells developed through the programme.
The team’s highly integrated approach will enable clinical observations to inform lab studies, whose findings will in turn be translated into novel preclinical and clinical studies.

Professor Catherine Bollard, Co-team Lead
Professor of Pediatrics and Microbiology, Immunology and Tropical Medicine
What excites me most about this approach is the energised, passionate group of people we’ve brought together, including world-renowned scientist and rising stars who will become the future leaders in the childhood oncology. That’s where out-of-the-box thinking comes from – suddenly, you find you’re learning from each other and working out how you can use each other’s special expertise to tackle a complex problem.
Professor Catherine Bollard is Professor of Pediatrics and Microbiology, Immunology and Tropical Medicine at The George Washington University and Director of the Center for Cancer and Immunology Research at the Children’s Research Institute at Children’s National Hospital. In these roles, Cath leads clinical and research efforts to fight cancer by strengthening the immune system using adoptive cell therapy. She has a long-standing research interest in gene and cell therapies, and her laboratory research has worked to translate novel cell therapeutics to the clinic.
For over 20 years, Cath has investigated the efficacy of tumor- and virus-specific T cells for cancer, giving her extensive experience in the evaluation of antigen-specific immune responses in humans. She has treated more than 200 patients with novel cell therapeutics at Baylor College of Medicine and Children’s National Medical Center, and as the sponsor/principal investigator on more than a dozen investigator-initiated IND studies using immune-based therapies, she is highly experienced in developing and running clinical studies as well as the development of translational bench to bedside studies. Cath joined Children’s National from the Baylor College of Medicine where she was a tenured professor in the Department of Pediatrics. Prior to that, she served as a Postdoctoral Fellow at Texas Children’s Hospital. She holds Bachelor of Medicine and Bachelor of Surgery degrees (MBChB) and a Doctor of Medicine (MD) from Otago University Medical School in New Zealand.
Organisation
Children's National Medical Center and The George Washington University

Martin Pule is Clinical Senior Lecturer in the Dept. of Haematology at UCL Cancer Institute and Honorary Consultant in Haematology at University College London Hospital. His research is focused on many aspects of genetic engineering of T-cells for cancer treatment, with a particular focus on CARs. He entered the T-cell engineering field in 2001 as a travelling Fulbright Scholar at the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston. Here, Martin Pule was the first to describe third generation forms of CARs and described one of the first clinical studies of CARs, which showed efficacy in a solid cancer. Martin Pule is Director of the UCL Chimeric Antigen Receptor (CAR) programme. He holds a Bachelor of Medicine and Bachelor of Surgery from University College Dublin and is a Fellow of the Royal College of Pathologists.
Organisation
University College London

Professor Marc-Olivier Coppens is a chemical engineer, who is globally recognised for pioneering nature-inspired chemical engineering (NICE). He developed a rigorous and systematic nature-inspired solution (NIS) methodology, which leverages fundamental mechanisms underpinning desired properties in nature, to solve challenging engineering problems within a practical context, from energy and scalable manufacturing to health and biomedical engineering.
Marc-Olivier is Ramsay Memorial Professor and Vice-Dean Engineering (Interdisciplinary, Innovation) at University College London (UCL). He leads the EPSRC (Engineering and Physical Sciences Research Council) “Frontier Engineering” Centre for Nature-Inspired Engineering at UCL and is a Fellow of the Royal Society of Chemistry, the Institution of Chemical Engineers (IChemE), the American Institute of Chemical Engineers (AIChE), Corresponding Member of the Saxon Academy of Sciences (Germany), and Qiushi Professor at Zhejiang University (China).
Organisation
University College London

Sergio Quezada is a Professor of Cancer Immunology and Immunotherapy at University College London Cancer Institute and Chief Scientific officer of Achilles Therapeutics. He earned his undergraduate degree in biochemistry from the P. Universidad Católica de Chile and a Ph.D. from Dartmouth Medical School in the US. In 2004, he joined the laboratory of the Nobel Laureate Prof James Allison at MSKCC, where he unveiled mechanisms underpinning the anti-tumour activity of anti CTLA-4 antibodies.
His work at UCL focuses in cancer immunology, tumour microenvironment, regulatory T cells and immune checkpoint blockade. His team’s research unveiled the critical role of Fc receptors and the tumour microenvironment in the mechanism of action of anti CTLA-4 antibodies, and he is an inventor of several key patents supporting the clinical development of antibodies targeting immune checkpoints including VISTA, ICOS and CD25. In the last few years, Prof Quezada and his team co-led the development of a first in class Treg-depleting anti-human CD25 antibody acquired by Roche in 2018 and is currently in clinical evaluation against solid cancers.
In addition to immune regulation, Prof Quezada’s research also aims to characterization and interrogate immune reactivity and function within the microenvironment of different human cancers, helping identify mechanisms of response and resistance to immunotherapy. His work in this area led to creation of a spin off company, Achilles therapeutics, a clinical stage company delivering personalised T cell therapies against cancer. In April 2020 Prof Quezada stepped in as Chief Scientific Officer of Achilles to lead the current and future scientific direction of Achilles.
Prof Quezada was a recipient of Dartmouth’s John W. Strohbern Medal for excellence in biomedical research, the Cancer Research Institute new investigator award, a CRUK Career Development Fellowship and a CRUK Senior Cancer Research Fellowship. In 2022 Prof Quezada was elected Fellow of the European Academy for Cancer Sciences
Organisation
University College London

Dr Kevin Litchfield trained in mathematics and bioinformatics, worked in the pharmaceutical industry at Novartis Oncology, completed a PhD in cancer bioinformatics, and completed his postdoctoral training with Prof. Charles Swanton at the Francis Crick Institute. Kevin is now a group leader at UCL Cancer Institute London, specialising in immune-oncology biomarker development and drug target identification.
Organisation
University College London

Professor Andrew Sewell is best known for his work on how T-cell receptors distinguish between healthy and diseased cells. He has recently described new ways by which some T-cell receptors can recognise most cancers from all people.
Organisation
Cardiff University

Prof. Terry Rabbitts is a molecular biologist who trained at the MRC Laboratory of Molecular Biology (LMB) in Cambridge as a post-doc with César Milstein. He succeeded Fred Sanger as head of the LMB Division of Protein and Nucleic Acid Chemistry, jointly with Cesar Milstein, and is currently Professor of Molecular Immunology at the Institute of Cancer Research, London. His work has centred on chromosomal rearrangements in antibody and T cell receptor genes and in cancer-associated chromosomal translocations. During this work, he has pioneered a number of technologies including cDNA cloning, chimaeric antibodies, gene targeting knock-in, intracellular antibody capture and antibody-derived compounds (Abd technology), including compounds to the “undruggable” RAS. Current work focusses on developing technologies to use intracellular antibodies and derived compounds as drugs against chromosomal translocation proteins and mutant RAS, aimed at leukaemia therapy.
He is a Fellow of the Royal Society, of the Academy of Medical Sciences, of the American Association for Cancer Research Academy and an EMBO Member. He has been awarded the Colworth Medal, the CIBA Medal and the Clotten Foundation Prize in recognition for his work on chromosomal translocation genes in cancer aetiology and novel approaches to cancer drug discovery.
Terry Rabbitts contributions to biotechnology include being chairman the SAB of Cambridge Antibody Technology until its IPO, of Quadrant HealthCare and of Kymab until their commercial acquisitions, and an SAB member of Domantis until its acquisition. He was a member of the Apustcan Board until its acquisition by Avacata. He is a co-founder of Orbit Discovery and Quadrucept Bio.
Organisation
The Institute of Cancer Research

Conrad Russell Y. Cruz, M.D., Ph.D. is an Associate Professor of Pediatrics and Microbiology, Immunology and Tropical Medicine at Children’s National Medical Center and the George Washington University. As one of the principal investigator for the Program for Cell Enhancement and Technologies for Immunotherapies (CETI), Dr. Cruz is developing cell based therapies that seek to enhance the immune system’s natural abilities to combat cancer and opportunistic chronic infections. Dr. Cruz received his MD from the University of the Philippines and his PhD from Baylor College of Medicine.
Organisation
Children’s National Medical Center

Dr Patrick Hanley is the Chief and Director of the Cellular Therapy Program and an associate professor of pediatrics at Children’s National Hospital and the George Washington University, respectively. He oversees processing for standard of care stem cell transplantation as well as the development, manufacture, and testing of novel cellular therapies and is responsible for seeking partnerships and commercialization of promising cell and gene therapies. Trained as an immunologist, Patrick has an extensive background and interest in cellular therapy and is passionate about improving regulations for cellular therapy, training the next generation of cell therapists, and facilitating the translation of new therapeutics. Over the past 15 years he has helped to translate more than 300 products on over 25 cell therapy protocols – ranging from mesenchymal stromal cells to cord blood virus-specific T cells and tumor-associated antigen specific T cells – into the clinic.
Patrick serves on the board of directors and as the chair of the education committee of the Foundation for the Accreditation of Cellular Therapy (FACT) and is an active cellular therapy and cord blood inspector. He co-founded and served as the inaugural co-chair of the Early-Stage Professionals committee and was elected as vice president, North America of the International Society of Cell and Gene Therapy (ISCT). He is the commissioning editor of the journal Cytotherapy and he serves on the editorial boards of the journals Cytotherapy, Frontiers in Immunology and Immunotherapy, and Molecular Therapy: Methods and Clinical Development. In 2017, along with Drs Catherine Bollard and Russell Cruz, he founded Mana Therapeutics, a biotech company aimed at educating immune cells and eliminating cancer. In his free time he enjoys playing soccer, cycling, cooking, and traveling.
Organisation
Children's National Medical Center

Amy Hont, M.D., is an attending physician in the Department of Hematology/Oncology and physician-scientist in the Center for Cancer and Immunology Research. Her research interest focuses on the use of targeted therapies, including immunotherapy, for patients with high-risk malignancies. In particular she investigates the optimization of adoptive cell therapy for patients with relapsed or refractory solid tumors, including modification of T cell products and the tumor microenvironment.
Organisation
Children's National Medical Center

Dr AeRang Kim is an Associate Professor of Pediatrics and Director of Clinical Research in the Division of Oncology and solid tumors attending at Children’s National Hospital in Washington, DC. Her research has focused on the clinical development of novel therapeutics for pediatric solid tumors, sarcomas, and tumor predisposition syndromes.
Organisation
Children's National Medical Center

Holly Jane Meany, M.D., is a pediatric oncologist at Children's National Hospital where she is leads the Solid Tumor Program. Dr. Meany's clinical research is focused on phase I clinical trials and pharmacology in the development of new agents for treating pediatric solid tumor malignancies.
Organisation
Children's National Medical Center

Dr Anqing Zhang is a faculty member within the Biostatistical Core of the Children’s National Hospital for the Center for Translational Research and an Assistant Professor of Pediatrics at School of Medicine and Health Sciences at George Washington University. She has a broad array of experience in developing statistical methodologies in designing preclinical and clinical trials (Phase I, II, III) and conducting clinical data analyses. Her research work focuses on developing optimal designs for clinical trials and drug development studies. She has developed adaptive two-stage optimal design for estimating multiple 𝐸𝐷𝑝𝑠 in dose-finding study. Her proposed design has been shown outperformed other traditional designs.
Anqing is currently collaborating on funded grant projects for the Program for Cell Enhancement and Technologies for Immunotherapy within the Center for Cancer and Immunology Research at Children’s National Hospital, providing statistical expertise in study design, data and safety monitoring, interim analysis and data analysis for the ongoing clinical trials. She also serves as a statistical mentor for junior faculty/fellows on their early career awards to help them with developing skills in the area of biostatistical methodologies.
Organisation
Children's National Medical Center

Professor Carolyn Bertozzi's research interests span the disciplines of chemistry and biology with an emphasis on studies of cell surface sugars important to human health and disease. Her research group profiles changes in cell surface glycosylation associated with cancer, inflammation and bacterial infection, and uses this information to develop new diagnostic and therapeutic approaches, most recently in the area of immuno-oncology.
Named a MacArthur Fellow in 1999, Carolyn has received many awards for her dedication to chemistry, and to training a new generation of scientists fluent in both chemistry and biology. She has been elected to the Institute of Medicine, National Academy of Sciences, and American Academy of Arts and Sciences; and received the Lemelson-MIT Prize, the Heinrich Wieland Prize, the ACS Award in Pure Chemistry, and the Chemistry of the Future Solvay Prize, among others.
In 2022, Carolyn jointly received the Nobel Prize for Chemistry, with Barry Sharpless and Morten Meldal, for pioneering click chemistry and using it to map glycans on the surface of living cells without disturbing cell function. To do this, she developed reactions called bio-orthogonal reactions, which are now being used to aid cancer drug development
Organisation
Stanford University

Professor Ansuman Satpathy is a physician-scientist who has pioneered the development and use of high-throughput genome sequencing technologies to study cancer immunology. His work has led to fundamental insights into how T cells - the cancer killing immune cell in the body - recognize and respond to cancer antigens and various forms of cancer immunotherapy.
Ansuman is an Assistant Professor in the Department of Pathology at Stanford University. He is an investigator in the Gladstone-UCSF Institute of Genomic Immunology, the Parker Institute for Cancer Immunotherapy, and the Stanford Cancer Institute. His honors include the Pew-Stewart Scholar Award in Cancer Research, the Lloyd J. Old STAR Award from the Cancer Research Institute, the Career Award for Medical Scientists from the Burroughs Wellcome Fund, and the Michelson Prize in Human Immunology. Ansuman is also a founder of multiple biotechnology companies focused on translational immunology and cancer immunotherapy.
Organisation
Stanford University

Dr Irving Weissman is the Founding Director of the Institute for Stem-Cell Biology and Regenerative Medicine at Stanford University (ISCBRM), Director of the Stanford Ludwig Center for Cancer Stem Cell Research, and former Director of the Stanford Cancer Center as well as the Immunology Program.
His research on hematopoiesis, hematologic malignancies and solid tumors has led to several discoveries and the development of new therapies. These include the isolation and transplantation of pure hematopoietic stem-cells (HSCs), isolation of hematopoietic progenitors and the development of non-toxic antibody-based conditioning for HSC transplantation. In acute myeloid leukaemia, he proposed and proved preleukemic development in clones of HSC accumulating one mutation at a time with the last mutation giveing rise to leukemic stem cells (LSC). Next, by comparing LSC to HSC, Irving discovered CD47 on leukemic stem-cells as a ‘don’t eat me’ signal used by leukemias and all human cancers tested to evade innate immunity. He showed that anti-CD47 blockade unleashes phagocytosis of cancer cells by macrophages, including brain microglia, and developed cancer immunotherapy, achieving remarkable results in phase-II clinical trials.
Irving is a member of the National Academy of Sciences, the Institute of Medicine at the National Academy, and the American Association of Arts and Sciences.
Organisation
Stanford University

Dr. John Maris is Giulio D’Angio Professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania and the Children’s Hospital of Philadelphia. He is a physician-scientist who has focused for over three decades on the childhood cancer neuroblastoma with the dual goals of improving patient outcomes and using the disease as a model to understand cancer in general. His group has discovered all the known neuroblastoma susceptibility genes and his group has also identified many of the oncogenic drivers of the disease. Dr. Maris has steadfastly sought to translate these discoveries to the clinic using precision medicine. Over the last decade he has led a multi-institutional St. Baldrick’s Foundation-Stand Up to Cancer Pediatric Cancer Dream Team project to bring the fields of genomics and immunology together to combat childhood cancers, and more recently a Beau Biden Moonshot Center Award to extend this rapidly evolving area of research. Dr. Maris is an internationally recognized practicing pediatric oncologist who cares for children with refractory neuroblastoma from around the world, typically in the context of early phase clinical trials. Dr. Maris has been continuously funded by the National Institutes of Health and many other funding bodies. He currently holds a National Cancer Institute Outstanding Investigator Award and has received several prestigious awards including election into the American Society of Clinical Investigation, the Oski award for outstanding pediatric oncologists, and the Berwick award at Penn for melding basic and clinical teaching, the William Osler Patient Oriented Research Award at Penn, and the AACR 2021 Team Science Award for his leadership in pediatric immunoncology research.
Organisation
The Children's Hospital of Philadelphia

My work converges at a longstanding interest is in developing safer and more effective therapies for cancer and a fascination with the function of the immune system. Following these interests over the past two decades, I have had the privilege of working with world leaders in antibody engineering at Genentech and later able complete my PhD work at the University of Pennsylvania where the pioneering clinical work on CAR T cells was first done. I have built experience across immunology, protein engineering, cancer biology, and computational biology, and have applied my expertise to understanding the immune interface at of peptide/MHC/receptor. Interactions at this immune interface have demonstrated the ability to cure at least subsets of patients through immune checkpoint inhibitors (ICIs) and adoptive transfer of tumor infiltrating lymphocytes (TILs). My work is focused on expanding the population of patients who can benefit from immunotherapies by characterizing and engineering interactions at this interface. To date, my work has resulted in the identification of novel targets that are highly specific to tumors, and CAR T cell therapies that can identify these targets in a highly selective manner. These CAR T cells completely eliminate tumors in mice and are slated for human clinical trials next year. My work in the coming years will focus on building on these methods and expanding their application to other cancers.
Organisation
The Children's Hospital of Philadelphia

Organisation
The Children's Hospital of Philadelphia

Organisation
The Children's Hospital of Philadelphia

Dr Anthony Sandler MBBCh, FACS, FAAP, is the Senior Vice President & Surgeon-in-Chief of the Joseph E. Robert Jr. Center for Surgical Care at Children’s National Hospital in Washington D.C and is the Director of the Sheik Zayed Institute for Surgical Innovation. He is the Diane and Norman Bernstein Chair in Pediatric Surgery and a Professor of Surgery and Pediatrics at George Washington University. Dr. Sandler is a thoracic and general pediatric surgeon with special interest in childhood solid tumors and operative repair of congenital anomalies.
Dr. Sandler's research interests include tumor immunology and tumor vaccine therapy, as well as the design and application of novel devices and technologies for surgical practice. Dr. Sandler has served and chaired multiple committees for the American Pediatric Surgical Association and is currently on the Board of Examiners for the Pediatric Surgery Qualifying examination. Dr. Sandler has over 160 peer reviewed publications in clinical and scientific medical journals and is an NIH funded investigator.
Organisation
Children’s National Hospital

Robbie Majzner is an Assistant Professor of Pediatrics at Stanford University School of Medicine who is focused on the development and deployment of immunotherapies for pediatric cancer. He received his MD from Harvard Medical School followed by training in pediatrics at New York Presbyterian-Columbia and pediatric hematology-oncology at the National Cancer Institute and Johns Hopkins. His work in the laboratory centers on engineering platform technologies to improve the efficacy of CAR T cells in solid tumors and overcome therapeutic resistance. Concurrently, he is focused on translating laboratory advances in innovative clinical trials for children with incurable cancers.
Organisation
Stanford University

Karen Page is a Professor of Mathematical Biology at UCL. She studied at Queens’ College, Cambridge (MA 1st class, MMath Distinction, 1992-1996). Her DPhil, on the topic of patterning in embryology, was completed in Oxford in 1999. She then went to the Institute for Advanced Study in Princeton as a postdoctoral fellow. There she studied evolutionary game theory and evolutionary dynamics. She joined the Department of Computer Science at UCL in 2001 as a Lecturer in Bioinformatics and subsequently moved to the Department of Mathematics in 2006. She was promoted to Reader in 2010 and Professor in 2015. During her time at UCL, she has worked on applying mathematical models to a variety of areas of biology, and is particularly interested in developmental biology, evolution and cancer.
Organisation
University College London

Working in the field of immunology for more than 20 years, Dr. Emmanuel Donnadieu has accumulated thorough experience in cellular imaging related to T cell physiology. He is particularly well recognized in the field of T cell migration and the role played by external factors controlling this process. His major contributions were the demonstrations of a defect in T cells to infiltrate tumors and the role of matrix fibers and macrophages in this process. His current projects aim at targeting the tumor microenvironment to improve T cell-based immunotherapies using relevant preclinical models. He is currently head of a team at the Cochin Institute, INSERM, in Paris.
Organisation
INSERM

Karin Straathof is a research group leader at the CRUK City of London Centre and honorary consultant paediatric oncologist at Great Ormond Street Hospital. Her research interest is T cell-based immunotherapy for childhood solid tumours. Her work includes one of the first phase I clinical studies of CAR-T cell therapy for children with relapsed or refractory neuroblastoma.
Organisation
University College London

Organisation
Imagine for Margo - children without cancer

Organisation
Pass The Smile

Organisation
Team Beans


Organisation
Team Finn Foundation

Sara Wakeling is Patient Advocate on the NexTGen team and the CEO and co-founder, of Alice’s Arc, a children’s cancer charity for rhabdomyosarcoma. Sara also holds a PPI/E Research Assistant role at the Louis Dundas Centre for Children’s Palliative Care at the UCL Great Ormond Street Institute of Child Health.
Organisation
Alice's Arc

