Meeting News

Abituzumab may be potential treatment for scleroderma

SAN DIEGO — Abituzumab has the potential to block TGF-beta-induced fibroblast to myofibroblast transition, and deter fibrosis development, according to Eileen Samy, PhD, a senior scientist specializing in immunology at EMD Serono Research and Development Institute Inc.

Speaking at the American College of Rheumatology Annual Meeting, Samy added that abituzumab thus has the potential to be an efficacious drug for the treatment of scleroderma.

“Abituzumab is pan alpha v integrin antibody, so therefore it blocks all integrins containing the alpha V chain, which is alpha V beta 3, alpha V beta 3, alpha V beta 5, alpha V beta 6 and alpha V beta 8,” she said. “In this study, we used a cell culture system to show the effect of blocking the fibroblast transition.”

To determine if abituzumab can block TGF-beta activation and fibroblast to myofibroblast transition in vitro, Samy and colleagues analyzed the expression of integrins and myofibroblast markers in human lung fibroblasts. They used reverse transcription polymerase chain reaction in both the presence and absence of abituzumab.

In addition, the researchers examined the ability of abituzumab to block fibroblast to myofibroblast transition in a co-culture of epithelial cells and fibroblasts, which would mimic the potential interaction in tissues undergoing fibrosis.

According to Samy, human lung fibroblasts express ITGB1>ITGB5>ITGB8>ITGB3. TGF-–induced fibroblast to myofibroblast transition caused an increase in the expression of ITGB5, and smaller increases in ITGB1 and ITGB3 expression. TGF-beta treatment increased myofibroblast marker genes in lung fibroblasts, and immunofluorescence staining revealed increased alpha V beta 5 and alpha-smooth muscle actin (alpha SMA) expression, she added.

The researchers found that abituzumab treatment of fibroblast cultures resulted in a reduction in the increased alpha SMA expression, as well as of IL-6 production and collagen gel contraction. According to Samy, this suggests abituzumab can block TGF-beta–induced fibroblast to myofibroblast transition. The co-culture of epithelial cells with fibroblasts resulted in induction of alpha SMA and multiple mRNA transcripts that are markers for fibroblast to myofibroblast transition, as well as increased IL-6 production. Abituzumab treatment resulted in the reduction of these markers, which Samy said is an indication that alpha V integrins play a role in fibroblast to myofibroblast transition.

“Overall, the conclusion is that abituzumab reduced TGF-beta–induced alpha-smooth muscle IL-6 and [fibroblast to myofibroblast transition]-related gene expression,” Samy said. “It also blocked the elevated expression of alpha-smooth muscle and other [fibroblast to myofibroblast transition]-related genes in the co-culture system, so therefore it may be an effective therapy for the treatment of systemic sclerosis and other fibrotic diseases.”

Reference:

Samy E. #774. Presented at: American College of Rheumatology Annual Meeting, Nov. 3-8, 2017; San Diego.

Disclosure: Samy reports employment with EMD Serono Inc.

SAN DIEGO — Abituzumab has the potential to block TGF-beta-induced fibroblast to myofibroblast transition, and deter fibrosis development, according to Eileen Samy, PhD, a senior scientist specializing in immunology at EMD Serono Research and Development Institute Inc.

Speaking at the American College of Rheumatology Annual Meeting, Samy added that abituzumab thus has the potential to be an efficacious drug for the treatment of scleroderma.

“Abituzumab is pan alpha v integrin antibody, so therefore it blocks all integrins containing the alpha V chain, which is alpha V beta 3, alpha V beta 3, alpha V beta 5, alpha V beta 6 and alpha V beta 8,” she said. “In this study, we used a cell culture system to show the effect of blocking the fibroblast transition.”

To determine if abituzumab can block TGF-beta activation and fibroblast to myofibroblast transition in vitro, Samy and colleagues analyzed the expression of integrins and myofibroblast markers in human lung fibroblasts. They used reverse transcription polymerase chain reaction in both the presence and absence of abituzumab.

In addition, the researchers examined the ability of abituzumab to block fibroblast to myofibroblast transition in a co-culture of epithelial cells and fibroblasts, which would mimic the potential interaction in tissues undergoing fibrosis.

According to Samy, human lung fibroblasts express ITGB1>ITGB5>ITGB8>ITGB3. TGF-–induced fibroblast to myofibroblast transition caused an increase in the expression of ITGB5, and smaller increases in ITGB1 and ITGB3 expression. TGF-beta treatment increased myofibroblast marker genes in lung fibroblasts, and immunofluorescence staining revealed increased alpha V beta 5 and alpha-smooth muscle actin (alpha SMA) expression, she added.

The researchers found that abituzumab treatment of fibroblast cultures resulted in a reduction in the increased alpha SMA expression, as well as of IL-6 production and collagen gel contraction. According to Samy, this suggests abituzumab can block TGF-beta–induced fibroblast to myofibroblast transition. The co-culture of epithelial cells with fibroblasts resulted in induction of alpha SMA and multiple mRNA transcripts that are markers for fibroblast to myofibroblast transition, as well as increased IL-6 production. Abituzumab treatment resulted in the reduction of these markers, which Samy said is an indication that alpha V integrins play a role in fibroblast to myofibroblast transition.

“Overall, the conclusion is that abituzumab reduced TGF-beta–induced alpha-smooth muscle IL-6 and [fibroblast to myofibroblast transition]-related gene expression,” Samy said. “It also blocked the elevated expression of alpha-smooth muscle and other [fibroblast to myofibroblast transition]-related genes in the co-culture system, so therefore it may be an effective therapy for the treatment of systemic sclerosis and other fibrotic diseases.”

Reference:

Samy E. #774. Presented at: American College of Rheumatology Annual Meeting, Nov. 3-8, 2017; San Diego.

Disclosure: Samy reports employment with EMD Serono Inc.

    See more from American College of Rheumatology Annual Meeting