by Mary Ann Liebert, Inc

Specificity and selectivity of anti-Siglec8 hybridoma supernatants assessed by Siglec8 enzyme-linked immunosorbent assay (ELISA). (A) ELISA detection of Siglec8 antibody binding to recombinant His-tagged human Siglec8 protein. 2E2 anti-Siglec8 antibody (2 µg/mL, GenScript, Piscataway, NJ) was used as a positive control for Siglec8 binding. Selective ELISA of Siglec8-specific antibodies showed no cross-reactivity toward closest Siglec family members (recombinant human Siglec-5 protein and recombinant human Siglec-7 protein) as assessed by ELISA. (B–E) Half-maximal effective concentration (EC50) determination for each of the purified Siglec8 antibody candidates (n = 19). The anti-Siglec8-2E2 antibody (GenScript, Piscataway, NJ) was used as a positive control. The numbers in panel are the means of the antibodies; the numbers in panels B–E are the lot numbers. Antibody 08C07 is lot 010. Credit: Human Gene Therapy (2024). DOI: 10.1089/hum.2024.165

A study published in Human Gene Therapy has involved the generation of a human monoclonal antibody (mAb) directed against human eosinophils. The heavy and light chains of that fully human anti-human eosinophil mAb were delivered via an adeno-associated virus (AAV)-based gene therapy to immunodeficient mice, where they suppressed levels of human eosinophils in vivo.

Chronic hypereosinophilia is defined as persistent elevated blood levels of eosinophils. It is associated with infiltration of eosinophils into the tissues and resulting organ damage by eosinophil release of toxic mediators.

“As a novel approach to treat chronic hypereosinophilia, we hypothesized that AAV-mediated delivery of an anti-human eosinophil antibody would provide one-time therapy that would mediate persistent suppression of blood eosinophil levels,” stated Ronald Crystal, from Weill Cornell Medical College, and co-authors of the study.

The investigators showed that in vivo gene therapy in mice mediated the destruction of human eosinophils and antibody-dependent cellular cytotoxicity activity against human eosinophils. They concluded that the anti-human eosinophil mAb “holds the potential to offer therapeutic benefit to patients with chronic hypereosinophilia.”

“This study highlights the potential for the gene therapy field to provide effective long-term therapies for chronic conditions, which currently require frequent treatments with painful and/or debilitating side effects,” says Managing Editor of Human Gene Therapy Thomas Gallagher, Ph.D., from the University of Massachusetts Chan Medical School.

More information: Maria Gioulvanidou et al, Vectorized Human Antibody-Mediated Anti-Eosinophil Gene Therapy, Human Gene Therapy (2024). DOI: 10.1089/hum.2024.165

Journal information:Human Gene Therapy

Provided by Mary Ann Liebert, Inc

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