Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.
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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 mantle cell lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia, many of which express the IgM type of BCR on their cellular surface.
Therefore, IgM is an attractive target for therapeutic antibodies 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 human leukocyte antigen (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 cell proliferation 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.”
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About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
Oncotarget is indexed and archived byPubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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