Case Studies

Our case studies provide technical details on some of our recent projects that have advanced medical research or pharmaceutical development
Use of Retrogenix cell microarray technology to confirm specificity of diagnostic molecules created using the NanoMab platform

High specificity to a primary target receptor is not only important when developing novel therapeutics, it may also be critical in the development of reliable diagnostic tools. Uniquely, for diagnostics that are intended to be physically administered to patients in order to detect and quantify disease in situ

Assessing mAb specificity prior to IND submissions

Ensuring that monoclonal antibodies are specific to a single, primary target receptor is increasingly being recognised as a critical step in the development of these essential biological therapies. Tissue cross reactivity (TCR) studies have traditionally been used to uncover potential off-target events that warrant further investigation. Despite TCR showing that binding occurs in certain tissues, which, in turn, may indicate an off-target issue…

Retrogenix data in regulatory applications

Data from Retrogenix specificity studies have been included in numerous regulatory applications. To help gain a better understand of how Retrogenix data can support IND and BLA submissions, we initiated a feedback process to find out how those molecules progress through to regulatory approval. Encouragingly, we found that 38% of the molecules submitted contained Retrogenix data only with a success rate of 90% across all submissions.

Screening the secretome for off-target binding

Off-target binding to secreted proteins has the potential to cause clinical toxicity or alter the pharmacokinetic profile of biotherapeutics in development. Here we describe the adaptation of the cell microarray technology – beyond the plasma membrane proteome – to screen for interactions with proteins that are usually secreted from the cell. This provides an even more powerful solution for off-target assessment of biotherapeutics…

Retrogenix identifies interactions mediated by post-translational modifications

Research aimed at understanding the mechanism by which one form of malaria specifically attacks the placenta in pregnant women has resulted in the discovery of a potential new therapy that could be effective in a wide range of cancers. Key interactions meditated via distinct chondroitin sulphate (CS) chains were detected by Retrogenix in the study showing the real advantage over traditional protein…

Correcting specificity in an antibody therapeutic

A recent publication describes how an anti-PD1 antibody, which caused the unique side-effect of capillary hemangioma in early phase clinical studies, was screened using Retrogenix technology and found to bind to off-target receptors that are biologically relevant to the formation of hemangioma. Subsequent molecular remodelling of the antibody not only eradicated the in vitro off-target binding but also led to increased potency in PD1/PD-L1 blockade…

Identification and validation of monoclonal antibody cross-reactivity

A single monoclonal test antibody – developed against a key GPCR target – was provided by the study sponsors along with an isotype-matched negative control antibody. An initial pre-screen was undertaken to determine the levels of background binding of the test antibody to untransfected HEK293 cells as well as its binding to cells over-expressing the known primary receptor. Binding was assessed using a…

Compugen study identifies key TIGIT family immune checkpoint pair

Data presented at a recent conference showcased the utility of the Retrogenix platform in identifying a key immune checkpoint pairing within the TIGIT family. This case study provides further details of how PVRL2 was identified as a specific cell surface binding partner for PVRIG which has presented new opportunities for the development of cancer immunotherapy treatments including potential combination therapies with current immune checkpoint blockers…

Identifying human receptors mediating viral infection using cell microarray technology

This case study describes the discovery of the specific human cell surface receptor for the Hom-1 virus, a member of the caliciviridae family of viruses that infect a broad range of animal hosts and are associated with various chronic and acute illnesses. The Retrogenix technology was used to screen Hom-1 virus-like particles (VLP) against extensive arrays of human plasma membrane proteins over-expressed in…

Retrogenix identifies cell surface receptor associated with malaria – Nature paper

Collaborating with the University of Copenhagen, Retrogenix was able to successfully identify a key cell surface receptor associated with a severe form of childhood malaria. This opens up exciting new possibilities for drug and vaccine treatments for the disease, which is currently responsible for around half a million deaths in Africa every year.

Unravelling the molecular mechanisms of pulmonary arterial hypertension

Researchers from the University of Sheffield, UK, have furthered their understanding of the molecular mechanisms of a fatal lung condition by using the Retrogenix cell microarray technology to identify human cell surface receptors for osteoprotegerin (OPG) – a secreted glycoprotein that is elevated in patients with the disease. The study sheds light on the signalling mechanisms through which OPG induces proliferation of pulmonary arterial smooth muscle cells.

Development of a whole CAR T cell specificity screen

Using cell lines provided by a clinical stage T cell therapy developer, Retrogenix has now developed an off-target profiling methodology which screens whole T cells for interactions against thousands of human plasma membrane protein targets to provide supporting data for pre-IND safety assessment. This case study describes the technology optimisation study and key results…

Discovering anti-cancer biologics using phenotypic screening and Retrogenix’s target deconvolution technology

Scientists used 3-D phenotypic screening to select novel antibodies that were functional against primary tumour cells. The Retrogenix technology then identified the specific cell surface antigen targets of the most promising phenotypic molecules…

Using the Retrogenix technology to uncover immune checkpoint receptors

Many key immune checkpoint interactions are not yet fully characterised – hampering efforts to discover and develop new, targeted immuno-therapies. Results from Retrogenix’s plasma membrane protein array screening demonstrate an efficient method for rapidly identifying specific ligand-receptor binding in human cells.

We were impressed with the power of the Retrogenix technology in terms of on/off target characterization of early drug candidates. Their quick turnaround time and excellent, proactive communication was a real pleasure.
Dr. Bernd Schlereth, Senior Director Nonclinical Safety, Covagen
Simcere logo
Aveo Oncology - The Human Response
Theraclone Sciences
Bluebird Bio
The Center for Infectious Disease Research
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Sanofi Logo
The University of Copenhagen
Lund University
NIH - National Institutes of Health
The University of Pennsylvania
Scripps Florida - The Scripps Research Institute
Peptinnovate Ltd - Unlocking Nature's Potential
The University of Sheffield
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Unum Theraputics Logo
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Molecular Partners Logo
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