AUTHOR=Ferrari Mathieu , Onuoha Shimobi C. , Fossati-Jimack Liliane , Nerviani Alessandra , Alves Pedro L. , Pagani Sara , Deantonio Cecilia , Colombo Federico , Santoro Claudio , Sblattero Daniele , Pitzalis Costantino 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.640070

DOI=10.3389/fimmu.2021.640070

ISSN=1664-3224

ABSTRACT=Biologic drugs, especially anti-TNF, are considered 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 current limitations of systemic administration, providing improved potency and safety. We developed a bispecific antibody (BsAb), combining human arthritic joint targeting, via the synovial specific scFv-A7 antibody, and TNFα neutralization, via the scFv-anti-TNFα of Adalimumab, with binding/blocking capacity comparable to Adalimumab-IgG. Tissue targeting capacity of the BsAb was confirmed on human arthritic synovium in vitro and in a synovium xenograft SCID mouse model. Peak graft accumulation occurred at 48h post-injection with sustained levels over Adalimumab-Ig for 7 days, and increased therapeutic effect, efficiently decreasing tissue cellularity and markers of inflammation with higher potency compared to standard treatment. This study provides the first description of a BsAb capable of drug delivery specifically to the disease tissue and strong evidence of improved therapeutic effect on human arthritic synovium, with applications to other existing biologics.