NexTGen
Co-led by Professor Catherine Bollard (Children's National Medical Center, USA) and Dr Martin Pule (University College London, UK).The challenge
NexTGen is tackling the 2020 solid tumours in children challenge.
Cancer is a leading cause of death by disease in children worldwide. 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. Despite this, developing specific treatments for children has also not been prioritised by biopharma. By building a deep understanding of how solid cancers develop in children, applying advanced cellular engineering technologies and performing progressive clinical studies, the team aims to produce effective CAR T-cell therapies for children with sarcomas and brain tumours. NexTGen’s goal is for these cutting-edge immunotherapies to become frontline treatments for children with these hard to treat cancers within the next decade, improving survival rates and mitigating the risk of lifelong treatment-related toxicities.
At a glance
NexTGen is funded by
Team and leadership
Co-led by clinician scientists:
The NexTGen team comprises experts in oncology, immunology, glycobiology, proteomics and mathematics across the UK, US and France.
Tackling the solid tumours in children challenge
Survival for some childhood solid tumours has seen little improvement for more than 30 years. Survivors can experience serious long-term effects of treatment, while children whose cancer returns often have few treatment options. NexTGen is addressing these challenges through five interlinked areas of work, connecting laboratory discoveries with clinical testing.
The NexTGen team aims to harness the potential of the immune system to treat these cancers, taking a comprehensive approach to discover new targets and develop and optimise novel CAR T-cell therapies for children with these diseases.
NexTGen are well underway with their challenge, with five interlinked aims central to their effort:
Identify surface and intracellular targets
Cancer vulnerabilities differ between childhood and adult tumours and novel targets for cell therapy in children are urgently needed. The team is exploring targets ranging from proteins and altered sugars on cancer cells to intracellular proteins and “dark antigens” produced from normally silenced regions of the genome. Its new HLA-Shuttle technology improves the presentation of antigens on the cell surface, helping researchers discover potential immunotherapy targets in cancers such as neuroblastoma that can otherwise evade immune recognition.
Overcome the immunosuppressive effects of the tumour environment
A major barrier to T-cell therapy is the tumour microenvironment, a complex multicellular milieu that can enable tumours to resist treatment. NexTGen is studying how the surrounding cells and signals in childhood solid tumours suppress immune responses. These insights are guiding the design of engineered T cells that can resist inhibitory signals or alter the tumour environment to make treatment more effective.
Component engineering and integration
Here, the team is developing receptors that precisely target the identified antigens, exploiting both classical and non-classical targets. The team has developed a strategy to help CAR T cells recognise cancers with low levels of their target antigen, a common route to treatment resistance. By anchoring the signalling protein SLP-76 to the T-cell membrane, researchers improved responses to low antigen levels and cancer-cell killing in preclinical leukaemia and myeloma models. The findings could inform the development of more effective therapies for childhood solid tumours.
Alongside this, work with team MATCHMAKERS has provided a new method to examine how T-cell receptors recognise their targets. NexTGen researchers also contributed to computational methods for designing antibodies against specific targets, expanding the tools available for immune engineering.
Develop new preclinical models
Most existing models of paediatric cancer do not incorporate the immune system, making it challenging to test the effectiveness of cell-based therapies. To address this, the team is optimising modelling approaches that better recapitulate tumour-immune-microenvironment interactions. These include tumour-on-a-chip technologies, patient-derived immune xenografts and mathematical models simulating the dynamics between tumour cells, immune cells and other components of the tumour microenvironment. Leveraging these advanced preclinical platforms will enable more accurate evaluations of the effectiveness of their novel T-cell therapies, guiding decisions on which candidates should proceed to clinical testing.
Perform clinical testing
n 2025, NexTGen launched three interlinked early-phase clinical trials at centres in the UK and US, testing engineered T-cell therapies for children and young people with difficult-to-treat solid tumours. The NexTGen patient advocates have also helped shape study design, ethics documents and communications materials. Findings from the trials will feed back into the team’s laboratory and preclinical research, supporting continued refinement of its therapies.
Looking ahead
NexTGen’s highly integrated bench-to-bedside strategy aims to accelerate the development of more potent and effective CAR T-cell products for childhood solid tumors. With its clinical programme underway, NexTGen is connecting advances in target discovery and T-cell engineering with studies in children and young people. The trials will provide crucial early evidence to guide further development, while ongoing laboratory research addresses barriers to effective treatment. Together, these efforts could bring more effective and less toxic immunotherapies closer to children with sarcomas and brain tumours.
To learn more, visit NexTGen's website, which is managed and updated by the team itself.
