Novel Bispecific Antibody for Synovial-Specific Target Delivery of Anti-TNF Therapy in Rheumatoid Arthritis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Mar 8

PMID 33679801

Citations 8

Authors

Mathieu Ferrari

Shimobi C Onuoha

Liliane Fossati-Jimack

Alessandra Nerviani

Pedro L Alves

Sara Pagani

Cecilia Deantonio

Federico Colombo

Claudio Santoro

Daniele Sblattero

Costantino Pitzalis

Affiliations

Soon will be listed here.

Abstract

Biologic drugs, especially anti-TNF, are considered as the gold standard therapy in rheumatoid arthritis. However, non-uniform efficacy, incidence of infections, and high costs are major concerns. Novel tissue-specific agents may overcome the current limitations of systemic administration, providing improved potency, and safety. We developed a bispecific antibody (BsAb), combining human arthritic joint targeting, the synovial-specific single-chain variable fragment (scFv)-A7 antibody, and TNFα neutralization, the scFv-anti-TNFα of adalimumab, with the binding/blocking capacity comparable to adalimumab -immunoglobulin G (IgG). Tissue-targeting capacity of the BsAb was confirmed on the human arthritic synovium and in a synovium xenograft Severe combined immune deficient (SCID) mouse model. Peak graft accumulation occurred at 48 h after injection with sustained levels over adalimumab-IgG for 7 days and increased therapeutic effect, efficiently decreasing tissue cellularity, and markers of inflammation with higher potency compared to the standard treatment. This study provides the first description of a BsAb capable of drug delivery, specifically to the disease tissue, and a strong evidence of improved therapeutic effect on the human arthritic synovium, with applications to other existing biologics.

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