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Recombinant mannan-binding lectin (MBL) for therapy
J C Jensenius1, P H Jensen, K McGuire
1Department of Medical Microbiology and Immunology, University of Aarhus, Denmark. j.c.jensenius@immunology.au.dk
Abstract:
Mannan-binding lectin (MBL) is a plasma protein involved in the innate immune response. It binds to a number of micro-organisms and promotes killing of these through complement activation either directly or through opsonization. Clinical evidence indicates that in a variety of situations genetically determined low MBL levels are associated with increased susceptibility to infections. Infusions of plasma-derived MBL into MBL-deficient individuals was found to be safe in preliminary trials, but we considered that sufficient production and product safety could only be achieved through synthesis of recombinant MBL. A transfected human cell line produces MBL showing the same biological activity as plasma-derived MBL, and an essentially identical profile on MS. The production has been scaled up and clinical trials will start this year.
Insights
Recombinant mannan-binding lectin (MBL), produced by a human cell line, demonstrates biological activity identical to plasma-derived MBL. This advancement paves the way for clinical trials in MBL-deficient individuals to combat infections.
Area of Science:
- Immunology
- Biotechnology
- Protein Therapeutics
Background:
- Mannan-binding lectin (MBL) is crucial for innate immunity, mediating pathogen recognition and clearance via complement activation.
- Genetic deficiencies in MBL correlate with heightened susceptibility to various infections.
- Previous trials using plasma-derived MBL showed safety but faced production challenges.
Purpose of the Study:
- To develop a safe and scalable method for producing biologically active MBL.
- To establish recombinant MBL (rMBL) as a viable therapeutic alternative to plasma-derived MBL.
- To prepare for upcoming clinical trials of rMBL.
Main Methods:
- A human cell line was transfected to produce MBL.
- The biological activity of the produced rMBL was assessed.
- Mass spectrometry (MS) was used to compare rMBL with plasma-derived MBL.
- Production was scaled up for clinical use.
Main Results:
- The transfected cell line successfully produced MBL with biological activity comparable to plasma-derived MBL.
- Mass spectrometry confirmed an essentially identical profile for rMBL and native MBL.
- Production scale-up was achieved, enabling further clinical development.
Conclusions:
- Recombinant MBL production using a transfected human cell line is feasible and yields a product with equivalent biological function.
- This method offers a scalable and potentially safer alternative for MBL replacement therapy.
- The successful scale-up and product characterization support the initiation of clinical trials for MBL-deficient individuals.