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Novel therapeutic bispecific antibodies for B-cell lymphoma

Novel therapeutic bispecific antibodies for B-cell lymphoma
B-cell depletion of BTA106 in cynomolgus monkeys. Credit: 2024 Ohashi et al.

A new research paper was published in Oncotarget entitled, "Novel therapeutic bispecific antibodies for B-cell lymphoma targeting IgM and other antigens on the B-cell surface."

The B-cell receptor regulates B-cell proliferation and apoptosis. Aberrations in BCR signaling are associated with the development and progression of B-cell malignancies, such as , diffuse large B-cell lymphoma, and , many of which express the IgM type of BCR on their cellular surface.

Therefore, IgM is an attractive target for against B-cell malignancies. However, soluble IgM competitively binds to anti-IgM antibodies in the serum, and these antibodies show insufficient cytotoxic activity. Thus, antibody therapy targeting IgM is hindered by the presence of soluble IgM in the blood.

In this new study, researchers Takahiro Ohashi, Sayuri Terada, Shinsuke Hiramoto, Yuko Nagata, Hirokazu Suzuki, Hitoshi Miyashita, Tetsuo Sasaki, Yasukatsu Tsukada, and Keiko Fukushima from ZENOAQ (Zenyaku Kogyo Co., Ltd.) used a bispecific antibody to address this problem.

"In this study, we aimed to produce IgM-dependent bispecific antibodies targeting IgM and the other B-cell antigens such as CD20, CD32b (FcγRIIB), CD79b, and (HLA)-DR using the Cys1m technology [10, 43–45]. Additionally, the correct IgG-like bispecific antibody structures were confirmed, and their efficacies in the presence of soluble IgM were analyzed."

The researchers generated bispecific antibodies bound to IgM and other B-cell antigens, such as CD20 and HLA-DR, using their own bispecific antibody-producing technology, Cys1m. These bispecific antibodies directly inhibited via cell-cycle arrest and apoptosis in vitro, although large amounts of soluble IgM were present. Additionally, a bispecific antibody bound to IgM and HLA-DR (BTA106) depleted B-cells in cynomolgus monkeys.

"These data suggest that anti-IgM/B-cell surface antigen-binding specific antibodies are promising therapeutic agents for B-cell malignancies. Moreover, the bispecific antibody modality can potentially overcome problems caused by soluble antigens."

More information: Takahiro Ohashi et al, Novel therapeutic bispecific antibodies for B-cell lymphoma targeting IgM and other antigens on the B-cell surface, Oncotarget (2024). DOI: 10.18632/oncotarget.28578

Journal information: Oncotarget
Provided by Impact Journals LLC
Citation: Novel therapeutic bispecific antibodies for B-cell lymphoma (2024, April 16) retrieved 29 May 2024 from
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