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BsAb Application in Pulmonary and Respiratory Disease

With our top antibody engineering platforms, Creative Biolabs can produce custom bispecific antibodies (BsAbs) for receptor signaling interference in the application of pulmonary and respiratory diseases.

Infection and inflammation are the main pathogenesis of pulmonary and respiratory diseases. Several pulmonary and respiratory diseases are caused or intensified by unwanted immune responses, excessive inflammation, and/or aberrant wound healing process. For example, Th2 and Th17 polarized immune responses is the main trigger of allergic asthma, while an aberrant wound healing process and associated inflammation in the pulmonary interstitium is believed to be the cause of idiopathic pulmonary fibrosis, a progressive fibrotic disease of the lungs. BsAbs can bind ligands or receptors and block unwanted signaling pathways and be useful in therapeutics.

Pulmonary and Respiratory Diseases Related Receptors

Intercellular and intracellular signaling networks integrate and distribute regulatory information and regulate biological responses to different stimuli. Signaling pathways are also involved in the progression of different kinds of pulmonary and respiratory diseases: allergic asthma is centered on Th2 and Th17 polarized immune responses; Th2 dependent asthma may be enhanced by pyrin domain containing 3 (NLRP3); production of IL17A/F and IL22 (RORγc-dependent) by T-cells and ILC3 drives severe neutrophilic asthma. Monospecific antibodies are popular drugs designed to block signaling mediators in the progression of diseases. However, many times cells have escape pathways due to biological redundancy. Being bispecific, BsAbs could be used to target a principal target as well as an escape pathway at the same time, or to block the same pathway at two points, thus improve therapeutic efficacy. BsAbs that block proinflammatory cytokines or factors involved in fibroblast can relieve even cure pulmonary and respiratory diseases.

 Schematic diagram of the two different pathways result in eosinophilic airway inflammation in asthma. (Brusselle, G. G., 2013)

Figure 1. Schematic diagram of the two different pathways result in eosinophilic airway inflammation in asthma. (Brusselle, G. G., 2013)

Examples of BsAb

As a specific example, TBTI (DVD)-IgG SAR156597 (from Serono) is designed to treat idiopathic pulmonary fibrosis and other fibrotic indications with the same underlying mechanism (e.g., scleroderma). DVD-IgG is manufactured by elongating an IgG molecule at its N-terminus with an additional variable domain of a second antibody, with the variable domains oriented in a tandem configuration. SAR156597 targets Th2 cytokines IL4 and IL13 at the same time, suppresses IL-4/IL-13-induced human fibroblast activation.

Schematic representation of the DVI-IgG antibody. (Spiess, C., 2015)

Figure 2. Schematic representation of the DVI-IgG antibody. (Spiess, C., 2015)

With years of dedicated work, Creative Biolabs becomes the leader in BsAb services. We provide professional services to engineer different formats of BsAbs to treat pulmonary and respiratory diseases.

References

1. Brusselle, G. G.; et al. Eosinophils in the spotlight: eosinophilic airway inflammation in nonallergic asthma. Nature medicine. 2013, 19(8): 977-979.
2. Spiess, C.; et al. Alternative molecular formats and therapeutic applications for bispecific antibodies.” Molecular immunology. 2015, 67(2): 95-106.

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