Researchers at Orbsen Therapeutics are using proprietary technology, including novel cell isolation platforms, GMP-compliant cell production, and biodistribution imaging, to better understand the distribution and potency of stromal cells once administered to patients and to further our understanding of how stromal cells control inflammatory diseases.

BREAST CANCER TEAM

In collaboration with Professor Michael Kerin and Professor Timothy O’Brien at NUI Galway, Orbsen Therapeutics’ Breast Cancer Group is using established and novel state-of-the-art breast cancer models to validate CD362 as a therapeutic target within the breast tumour microenvironment (TME). Targeting the TME in breast cancers is difficult due to a lack of functional proteins that identify heterogeneous stromal cells in vivo. While ablation of FAP+ stromal cells reduces tumour size, this causes anaemia and cachexia due to targeting of healthy stromal cells. Thus, stromal ablation may have unwanted adverse systemic effects. Our group targets pro-tumourigenic factors that stromal cells are releasing, such as CD362. This may be a safer, more effective strategy. Our data suggests CD362 is a functional component of the TME creating an immune-suppressive/pro-migratory environment.

EV CLUSTER

EVs are small extracellular vesicles released from most cell types in the body, including mesenchymal stromal cells, and are emerging as a potential alternative to some stromal cell-derived therapeutics. These vesicles act as messengers between cells and can deliver important cellular cargo such as enzymes, mRNA, miRNA and immuno-regulatory proteins. The mechanism of action of EVs is not fully understood, but they appear to function in a similar manner to that of whole cells. The EV Cluster focuses on developing a novel therapy using ORBCEL-EV™, purified stromal cell-derived extracellular vesicles, elucidating and characterising the molecular mechanisms behind EVs, using techniques such as Western blotting, ELISA, enzymatic assays, flow cytometry, TEM and T-cell proliferation assays, to develop them as a therapy by testing in various in vivo disease models.

PROCESS DEVELOPMENT TEAM

The focus of the Process Development Team is to improve and optimise all aspects of the process design for our current cell therapies- ORBCEL-M™, ORBCEL-C™ and ORBCEL-A™, and any future cell therapies. This includes improving upstream processes from cell source to tissue sample collection and cell isolation strategies. We evaluate novel technologies which allow development of a closed-process of our therapeutic products e.g. Miltenyi Tyto a novel GMP cell sorter. We aim to improve cell isolation techniques, purity and batch-to-batch consistency of ORBCEL™ therapies. We are responsible for all downstream processing from continued cell culture monitoring, cell characterisation (growth kinetics, surface marker expression, functional assays such as immune suppression assays) right through to how ORBCEL™ is preserved for shipping to clinical trial sites. The team are also key to providing Orbsen technology transfer, training and advice on our stromal cell products to our collaborators. The Process Development Team works collaboratively with our EU consortia partners to advance our knowledge of CD362+ stromal cells in both pre-clinical and clinical applications.

IMMUNOLOGY GROUP

In general, the transplantation of donated cells or organs to unrelated recipients will cause rejection. Combatting the adverse immune reaction is a critical challenge within the field of cell therapy. The Immunology Group at Orbsen Therapeutics aims to achieve a better understanding of the immune-modulatory properties induced by stromal cells, and examines the persistence of stromal cells after administration, which may correlate to efficacy. We are focused on different approaches to avoid the rejection of stromal cells, and perform physiological and pathological analyses to correlate the efficacy of ORCEL™ cells. These factors are critical for the success of the cell therapy treatment.