Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb 20.
doi: 10.1111/all.16509. Online ahead of print.

Dual Inhibition of Mast Cells and Thymic Stromal Lymphopoietin Using a Novel Bispecific Antibody, CDX-622

Michael B Murphy  1 , Laura Vitale  1 , Thomas O'Neill  1 , Deena M Maurer  1 , Linda Malenchek  1 , Andrea Crocker  1 , Colleen Patterson  1 , Laura Mills-Chen  1 , Virginia Saley  1 , Nicole M Antczak  1 , James M Boyer  1 , Kelly M McManus  1 , Noe Rico Montanari  1 , Russell A Hammond  1 , Joel Goldstein  1 , Lawrence J Thomas  1 , Tibor Keler  1 , Diego Alvarado  1
Affiliations

Dual Inhibition of Mast Cells and Thymic Stromal Lymphopoietin Using a Novel Bispecific Antibody, CDX-622

Michael B Murphy et al. Allergy. .

Abstract

Background: Mast cells (MCs) respond to an array of allergens that drive allergic and inflammatory diseases. Stem cell factor (SCF), the ligand for the receptor KIT, is required for MC survival and function. Thymic stromal lymphopoietin (TSLP) is an alarmin that promotes Type 2 inflammation in asthma and other inflammatory diseases. We describe CDX-622, a bispecific antibody (bsAb), that targets both SCF and TSLP to neutralize these distinct cytokines.

Methods: The bsAb CDX-622 was developed from novel antagonist monoclonal antibodies (mAbs) to SCF (SCF-12) and TSLP (1D10). CDX-622 encodes the full-length 1D10 mAb and the single-chain variable fragment of SCF-12, linked to the C-terminus of the 1D10 heavy chain. CDX-622 was modified to prevent Fcγ receptor interactions and enhance FcRn binding. CDX-622 was tested using in vitro assays of MC and dendritic cell (DC) activation, an ex vivo human skin model, and in vivo studies in nonhuman primates.

Results: Novel SCF and TSLP mAbs with neutralizing activity were generated. The bsAb CDX-622 potently inhibited SCF-driven MC degranulation and TSLP-mediated CCL17 release by DCs. In human skin samples treated with SCF and TSLP, CDX-622 markedly reduced proinflammatory, MC, and DC-related RNA signatures. Additionally, CDX-622 and SCF-12 mAb administered to cynomolgus macaques (Macaca fascicularis) had a profound effect on MCs without any observed toxicity.

Conclusions: CDX-622 is a potent inhibitor of MCs through the neutralization of SCF and effectively blocks Type 2 inflammatory responses driven by TSLP. Dual inhibition of these cytokines may lead to improved clinical outcomes in certain inflammatory disorders.

Keywords: CDX‐622; SCF; TSLP; bispecific antibody; mast cell.

PubMed Disclaimer

References

    1. P. Rider, Y. Carmi, and I. Cohen, “Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations,” International Journal of Cell Biology 2016 (2016): 9259646, https://doi.org/10.1155/2016/9259646.
    1. J. Ma, Y. Mo, M. Tang, et al., “Bispecific Antibodies: From Research to Clinical Application,” Frontiers in Immunology 12 (2021): 626616, https://doi.org/10.3389/fimmu.2021.626616.
    1. Q. Zhao, “Bispecific Antibodies for Autoimmune and Inflammatory Diseases: Clinical Progress to Date,” BioDrugs 34, no. 2 (2020): 111–119, https://doi.org/10.1007/s40259‐019‐00400‐2.
    1. S. N. Abraham and A. L. St. John, “Mast Cell‐Orchestrated Immunity to Pathogens,” Nature Reviews. Immunology 10, no. 6 (2010): 440–452, https://doi.org/10.1038/nri2782.
    1. A. M. Piliponsky and L. Romani, “The Contribution of Mast Cells to Bacterial and Fungal Infection Immunity,” Immunological Reviews 282, no. 1 (2018): 188–197, https://doi.org/10.1111/imr.12623.

Grants and funding

LinkOut - more resources