Discovery and characterization of COVA322, a clinical-stage bispecific TNF/IL-17A inhibitor for the treatment of inflammatory diseases

Silacci, Michela; Lembke, Wibke; Woods, Richard D.; Attinger-Toller, Isabella; Baenziger-Tobler, Nadja; Batey, Sarah; Santimaria, Roger; Bey, Ulrike von der; Koenig-Friedrich, Susann; Zha, Wenjuan; Schlereth, Bernd; Locher, Mathias; Bertschinger, Julian; Grabulovski, Dragan

doi:10.1080/19420862.2015.1093266

Cited by 84 publications

(46 citation statements)

References 26 publications

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“…This has been shown with small peptides 86 and recently also with alternative scaffold proteins. 87, 88 Affibody molecules have been demonstrated to be useful as molecular specifiers for antibodies in several labs, including our own, and more than six different Affibody molecules have been combinatorially fused with antibodies to form functional multispecific proteins called ‘AffiMabs'. 87, 89 There are various formats of multispecific antibodies described which have quite different structures from the canonical IgG format.…”

Section: Affimabsmentioning

confidence: 99%

Affibody molecules as engineered protein drugs

Frejd

Kim²

2017

Exp Mol Med

175

147

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Affibody molecules can be used as tools for molecular recognition in diagnostic and therapeutic applications. There are several preclinical studies reported on diagnostic and therapeutic use of this molecular class of alternative scaffolds, and early clinical evidence is now beginning to accumulate that suggests the Affibody molecules to be efficacious and safe in man. The small size and ease of engineering make Affibody molecules suitable for use in multispecific constructs where AffiMabs is one such that offers the option to potentiate antibodies for use in complex disease.

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Section: Affimabsmentioning

confidence: 99%

Affibody molecules as engineered protein drugs

Frejd

Kim²

2017

Exp Mol Med

175

147

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“…Fynomers are small (6 kDa) engineered binding proteins that are derived from the SH3 domain of the Fyn kinase [16][17][18][19][20][21]. Fynomers can be genetically fused to different termini of antibodies resulting in bispecific proteins, termed FynomAbs, with different architecture, depending on the Fynomer fusion site.…”

Section: Introductionmentioning

confidence: 99%

Bispecific CD3/HER2 Targeting FynomAb Induces Redirected T Cell-Mediated Cytolysis with High Potency and Enhanced Tumor Selectivity

et al. 2015

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CD3 bispecific therapies retargeting T cells to tumors have recently demonstrated striking activity in patients. Several CD3 bispecific antibodies directed against various tumor targets are currently being investigated in the clinic across different tumors. One limitation of these therapies is the risk of target-related toxicity due to low-level expression of tumor antigen in normal tissue. In this study we have engineered a bispecific CD3/HER2 FynomAb, COVA420, which redirects T cells with high potency and selectivity to tumor cells with high HER2 expression in vitro and in vivo. COVA420 activity depends on high HER2 density as no activity was observed on cells with lower HER2 levels as found in human normal tissue. These results suggest that COVA420 may spare normal tissue expressing low levels of HER2 while still having uncompromised efficacy on tumor cells OPEN ACCESSAntibodies 2015, 4 427 with high HER2 expression. This concept may be applied to other cancer antigens that otherwise cannot be targeted by T cell redirecting approaches, and may therefore expand the applicability of CD3 bispecific FynomAbs to a larger number of solid tumors.

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“…One possible approach is to enhance proinflammatory cytokine inhibition by simultaneous targeting of more than one cytokine. This possibility is currently under evaluation in a clinical trial for the treatment of psoriasis with the bispecific TNF/IL-17 fusion antibody [89]. Other groups are exploring a more selective targeting approach by inhibiting only part of the signaling cascade initiated by a given cytokine.…”

Section: Discussionmentioning

confidence: 99%

Can we design a better anti-cytokine therapy?

Drutskaya

Efimov

Kruglov

et al. 2017

Journal of Leukocyte Biology

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Cytokine neutralization is successfully used for treatment of various autoimmune diseases and chronic inflammatory conditions. The complex biology of the two well-characterized proinflammatory cytokines TNF and IL-6 implicates unavoidable consequences when it comes to their global blockade. Because systemic cytokine ablation may result in unwanted side effects, efforts have been made to develop more specific cytokine inhibitors, which would spare the protective immunoregulatory functions of a given cytokine. In this article, we review current research and summarize new strategies for improved anti-TNF and anti-IL-6 biologics, which specifically target only selected parts of the signaling cascades mediated by these ligands.

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Discovery and characterization of COVA322, a clinical-stage bispecific TNF/IL-17A inhibitor for the treatment of inflammatory diseases

Cited by 84 publications

References 26 publications

Affibody molecules as engineered protein drugs

Affibody molecules as engineered protein drugs

Bispecific CD3/HER2 Targeting FynomAb Induces Redirected T Cell-Mediated Cytolysis with High Potency and Enhanced Tumor Selectivity

Can we design a better anti-cytokine therapy?

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