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Team

NexTGen

Challenge

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

Founders' logos
Professor Catherine Bollard

Professor Catherine Bollard, Co-team Lead

Professor of Pediatrics and Microbiology, Immunology and Tropical Medicine

NexTGen

Dr Martin Pule

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:

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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:

  1. 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.

  1. 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.

  1. 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.

  1. 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.

  1. 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

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
Dr Martin Pule
Professor Marc-Olivier Coppens
Professor Sergio Quezada
Dr Kevin Litchfield
Professor Andrew Sewell
Professor Terry Rabbitts
Dr Conrad Russell Cruz
Dr Patrick Hanley
Dr Amy Hont
Dr AeRang Kim
Dr Holly Meany
Dr Anqing Zhang
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Dr Ansuman Satpathy
Dr Irving Weissman
Dr John Maris
Dr Mark Yarmarkovic
Dr Nik Sgourakis
Dr Patrick Grohar
Dr Nitin Agrawal
Dr Robbie Majzner
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Dr Emmanuel Donnadieu
Karin Straathof
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Gavin Lindberg and his son Evan