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Boan Biotech Publishes Results of Anti-CD25 Antibody Research in Nature Sub-Journal

2021.11.25 | Boan Biotech,Shandong Boan Biotech, Boan Innovative Antibodies,Boan Biosimilar

The findings about BA1106, a fully human monoclonal anti-CD25 antibody developed by Boan Biotech, a subsidiary of Luye Pharma Group, were published in Scientific Reports, which is a journal of the Nature Portfolio. Scientific Reports is the sixth most-cited journal in the world, with more than 540,000 citations in 2020. 

 


 A  screenshot of the paper(Source : Scientific Reports)

 

CD25, also known as Interleukin-2 receptor alpha (IL-2Rα) chain, is highly expressed on tumor regulatory T cells (Treg cells). Treg cells inhibit a variety of immune cells, which is an important factor in the poor prognosis of most solid tumors. Therefore, eliminating Treg cells in tumor microenvironment becomes an important antitumor immunity strategy.

As one of the specific markers on the surface of Treg cells, CD25 is a potential target for Treg deletion. Taking advantage of the anti-CD25 antibodies' specificity to eliminate Treg cells and inhibit immunosuppression is an important antitumor treatment strategy. However, developing anti-CD25 antibodies faces two major problems at present: First, the mediation function of Fc is limited, and as a result, it only works in early-stage tumor models, but doesn't work in late-stage tumor models; second, the activation of the IL-2R signaling pathway by IL-2 is blocked, leading to poor antitumor performance.

The anti-CD25 antibodies obtained by Boan Biotech have a better efficacy for both early-stage and late-stage tumors, and demonstrate a good synergy when used in combination with an anti-PD1 antibody: they can basically clean up all the established tumors in an MC38 colon cancer model. Meanwhile, they don't block the activation of the IL-2R signaling pathway by IL-2, and have a moderate and specific blocking effect on Treg cells. The detailed findings are as follows:

Two anti-CD25 antibodies (BA9 and BT942/BA1106) were obtained based on the company's human antibody transgenic mouse BAhuMabTM and phage display technology. Both of them demonstrated good specificity to bind with CD25 and high activity in blocking CD25, without blocking the activation of the IL-2R signaling pathway by IL-2. Animal tests showed that both of them had a significant efficacy in both early-stage and late-stage tumor models.
 
BT942 demonstrated weaker affinity and ADCC activity than BA9 in vitro, but a stronger in vivo antitumor effect. This might be related to the weaker ability of BT942 to delete immune effector cells.
 
In the mouse MC38 colon cancer model, the combination of BT942 and anti-PD1 produced a synergy and demonstrated a better therapeutic effect. It had no obvious toxic and side effects on the mouse whether used alone or in combination with anti-PD1.
 
BT942 showed a bi-exponential serum concentration–time profile in cynomolgus monkeys. The antibody had a long half-life and good in vivo stability.
 
By analysing the crystal structure of CD25-IL-2-BT942 Fab complex, we found that BT942 and IL-2 bind to CD25 on two opposite sides. This is consistent with the observation in vitro that BT942 doesn't interfere with the IL-2 signalling pathway. 
"Based on the research data obtained till now, we found that BA1106 moderately eliminates Treg cells, and inhibits immunosuppression in tumor microenvironment without blocking the IL-2 signalling pathway, and can be used in combination with anti-PD1, so it is expected to recover the resistance of the current therapy based on anti-PD1 to some extent, and to become a promising antitumor therapy," said Dr. Dou Changlin, the corresponding author of this paper, who is also the President and COO of Boan Biotech. "BA1106 currently leads the way among anti-CD25 antibodies with this acting mechanism," he added. "We believe that, with further development in the future, BA1106 will become another major therapy of Boan Biotech for treating solid tumors, to form a strong portfolio along with our 10+ other innovative antibody candidates."

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