LIfT BioSciences N-LIfT cell therapy shows complete and superior cell killing in solid tumour organoids compared to Keytruda
Research reinforces the value of using Tumouroid models as efficacy indicators for IND submissions to accelerate getting potentially curative innate cell therapies to patients
London, 6 April 2022 –LIfT BioSciences, (‘LIfT’ or ‘the Company’), a biotech bringing to market a first-in-class allogeneic innate cell therapy, today announces that N-LIfT, its Neutrophil-based Leukocyte Infusion Therapy, showed potent tumour cell killing in a lung Tumouroid model (SC-NSCLC), with significant superiority over current standards of care, Keytruda and Cisplatin. Non-Small Cell Lung Cancer (NSCLC) kills more people than any other cancer and the Squamous Cell (SC) variant has poorest survival due to the ineffectiveness of current treatment options.
Current regulatory standards require researchers to demonstrate efficacy in animal models before a new therapy can gain approval, or investment, to go into humans in a clinical trial. However, despite recent advances in modelling neutrophil function in vivo, there is to date no validated animal model that can faithfully recapitulate human neutrophils maturation and migration. LIfT, therefore, focused on a new type of ex vivo model called Tumouroid, or organoid tumour model. Whilst the use of Tumouroids to test new therapies is a relatively new concept, there is growing scientific evidence that Tumouroids offer a far compelling predictive power (up to 80-90%) in solid tumour models for how such a therapy will go on to perform in patients.
A Tumouroid is when cells extracted from a patient’s tumour are cultured into a suspended 3D model to create 3D tumour fragments. The level of tumour killing can then be more accurately measured, using florescent markers and pigments markers, than would be possible in the body, and, importantly, without the risks to the patient associated with testing a new therapy.
The research was conducted in partnership with Champions Oncology in a non-small cell lung cancer (NSCLC) squamous cell Tumouroid and showed that N-LIfT completely destroyed the tumour to the point that it lost all structural integrity, which in-vivo would result in it disintegrating in the body. Furthermore, N-LIfT showed complete superiority to Keytruda, a gold-standard treatment for NSCLC, in Tumouroid reduction, as observed by fluorescent intensity. See fig 1 & 2.
Alex Blyth, Chief Executive Officer of LIfT BioSciences, commented: “Non-small cell lung cancer is one of the biggest killers in cancer, with squamous cell being the most difficult to treat. As such, there is a very high unmet need for new therapies and so we are very pleased to see these results demonstrating the ability of our flagship N-LIfT cell therapy to kill solid tumour organoids, outperforming Keytruda the current standard of care, to show that N-LIfT could potentially treat patients who currently have few remaining options.”
“There as a new wave of very promising human innate cell therapies like N-LIfT trying to get to patients that are not optimally represented in a mouse that does not have the right chemokines and growth factors and a potentially competing innate immune system that attacks the non-mouse cell therapy and cannot be completely depleted. Retrospective analysis in this area suggests that the new Tumouroid models have ten times the power to predict the efficacy that would then be seen in humans in clinical trials. I think once you have shown safety in mice as we have been, regulators now need to show flexibility in what models they accept for assessing efficacy specifically for IND submissions, so that they can speed up getting these promising therapies to save the lives of millions of patients with cancer who otherwise may have died waiting for breakthrough therapies like this.”
Ronnie Morris, MD, CEO of Champions Oncology states, “Our patient-derived xenograft organoid (PDXO) co-culture platform is an innovative platform that enables our partners to test their immunotherapy candidates in a system that recapitulates the tumour microenvironment, while preserving characteristics of the patient tumour and immune-tumour cell interactions in an ex vivo setting. LIfT BioSciences’ innate cell therapy results in our co-culture platform demonstrate that in the absence of an appropriate in vivo model system, sophisticated ex vivo platforms can offer an alternative solution for assessing therapeutic efficacy of next-generation cell therapy products.”
The organoids were patient-derived xenografts (PDXs) that recreate most of the key cell-to-cell and cell-to-matrix interactions through culturing in a mouse. Tumouroids are considered to be superior to conventional 2D assays in their ability to imitate the results you might expect to see in the human body.
About LIfT BioSciences:
LIfT Biosciences is a Biotech bringing to market a 1st in class allogeneic innate cell therapy called Neutrophil Only Leukocyte Infusion Therapy (N-LIfT). N-LIfT uses a special type of N1a neutrophil with special cancer killing and immune recruitment capabilities. Our vision is to develop the world’s first cell bank of mass produced ‘cancer killing neutrophils’ to deliver a portfolio of immuno-oncology cell therapies for delivering complete remission in all solid tumours. LIfT BioSciences was founded by Alex Blyth following the death of his mother to pancreatic cancer.
Fig 1: CTG-3493 PDX Tumouroid Model images under confocal microscopy using fluorescent dyes to identify different cell types to measure cancer cell killing
Fig 2. The relative percent change in fluorescence intensity, comparing N-LIfT to control and in a separate study Keytruda dose escalation compared to isotype control in the presence of autologous tumour infiltrating lymphocytes.
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