Evaluation of a first-in-class neutrophil-based immunotherapy platform for solid tumour indications in novel translational in vivo models.

LIfT Biosciences Ltd (LIfT) is a disruptive biotech bringing to market a first-in-class immunomodulatory alpha neutrophil (IMAN) cell therapy designed to overcome the limitations of current immunotherapies in solid tumours. LIfT's ground-breaking IMANs not only directly kill tumour cells in an innate antigen-independent manner, but recruit and modulate recipients' cytotoxic effector cells, such as T cells and NK cells, to give a durable response and long-lasting anti-tumour immunity. LIfTs first generation IMANs are manufactured from the haematopoietic stem cells (HSCs) of donors who possess exceptionally cytotoxic neutrophils. IMANs are generated using LIfTs proprietary _Neutrophil-based Leukocyte Infusion Therapy_ (N-LIfT) platform, with future iPSC-derived and gene engineered products in the pipeline.

The aim of this collaborative project between LIfT Biosciences and the University of Cambridge's Saeb-Parsy Lab (SPL) is to explore and investigate the application of IMAN cell therapy products in their various iterations in the cutting edge humanised _in vivo_ model systems developed at SPL, with particular focus on analysing the immunomodulatory and cytotoxic properties of IMANs in the context of tumour-bearing humanised mice.

Fundamental to IMANs mechanism of action (MoA) is their ability to modulate the hostile solid tumour microenvironment (TME). Standard _in vivo_ tumour models in immunodeficient mice lack the necessary human immune system components to investigate recipient immunomodulation by therapeutics, and thereby underplay the effectiveness of cell therapy modalities with this MoA by only assaying direct cytotoxicity. Additionally, SPL's humanised models utilise xenografted patient-derived tumour material (PDX), which allows a closer approximation of tumour architecture and component subsets that comprise the solid TME, and which are classically hostile to cell therapy infiltration and efficacy. The SPL humanised _in vivo_ models represent the currently achieved experimental apotheosis in terms of _in vivo_ modelling of the TME as would be encountered by IMANs during human clinical trials.

The Innovate UK Biomedical Catalyst funding would allow the project team to perform ground-breaking _in vivo_ (and associated _in vitro_) activities to explore the impact of IMAN cell therapies in solid tumour indications. State-of-the-art -omics techniques will be employed to generate a holistic view of IMANs potential in solid tumours, unveiling biomarkers for both safety and efficacy of IMANs for future clinical research.