Science
Our approach
Targeting malignant and inflamed tissue with soluble TCRs
TCR-based therapies are an emerging class of drugs leveraging highly specific recognition of tumour and tissue antigens to enable precision immunotherapy.
In oncology, soluble TCR approaches provide a unique mechanism of action that addresses many obstacles associated with targeting solid tumours, including:
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Targeting of intracellular antigens
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High-affinity binding to low-copy number peptide targets
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Tumour-targeted biodistribution
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Sustained recruitment of effector immune cells
In immune-mediated disease, soluble TCRs enable high affinity targeting of tissue antigens to suppress the immune system at the site of disease, facilitating:
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Biodistribution targeted to inflamed tissues
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T cell inhibition at the site of inflammation
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Blockade of autoantigen recognition
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Long serum half-life for less frequent dosing
Combining protein engineering and AI to rapidly deliver soluble TCR engager drugs
Despite their therapeutic potential, soluble TCR therapies, pose a development challenge requiring multiparameter protein engineering to identify stable, highly potent TCRs that engage their targets with no relevant off-target activity.
Engimmune’s proprietary AI-guided platforms accelerate the development of stable, soluble, multi- specific TCRs with extremely high affinity for their target antigens. We couple protein engineering with machine learning and innovative high-throughput solutions to rapidly deliver specificity- and affinity-enhanced soluble TCRs (specTRs) in oncology and inhibitory specTRs (inspecTRs) in immune-mediated disease.
Our specTR and inspecTR molecules are designed using a biology-driven approach and optimised across multiple parameters, including affinity, manufacturability, function and safety, to achieve a more efficient redirection of antitumour immunity or tissue-targeted immune suppression.
Safety first
Our unique technologies enable the identification of potential off-target effects at the start of the engineering process, resulting in early identification of highly de-risked candidates. We call this approach “specificity-guided affinity maturation,” which greatly increases both the speed and efficiency of clinical candidate selection activities.
Maximising efficacy through biology-driven design
The potency of soluble TCR engagers in oncology is affected by T cell fitness and the efficacy of TCR engagers in immune-mediated indications is influenced by the phenotype of activated T cells driving the disease. Engimmune is leveraging its advanced AI-guided protein engineering platforms to design molecules that interact with multiple receptors on the engaged T cell. In oncology, trispecific specTRs co-ligating CD3 and a second co-stimulatory receptor enhance potency of exhausted T cells, while in immune-mediated disease, inspecTRs combining multiple immunoligands offer the possibility to more potently inhibit pathogenic T cells.