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Ofatumumab and Granzyme B as immunotoxin against CD20 antigen

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Abstract

Anti‐CD20 antibodies such as ofatumumab has demonstrated efficacy in relapsed/refractory chronic lymphocytic leukemia, are among the most successful therapies to date. In this study, we have designed an immunotoxin composed of Granzyme B and the high affinity variant of Ofatumumab. Different simulation software applied to explore the structure of Granzyme B, a serine protease in cytotoxic lymphocytes granules as an apoptosis mediator was attached to its specific antibody structure (Ofatumumab) via an adaptor sequence. The accuracy, energy minimization and characterization of biological properties of the final structure were evaluated. Our computational outcomes indicated that the employed method for structure prediction has been successfully managed to design the immunotoxin structure. The precise and accurate design of the immune-therapeutic agents against cancer cells can be confirmed by employment of in-silico approaches. Consequently, based on this approach we could introduce a capable immunotoxin which specifically targeting CD20 in an accurate orientation and initiates cancer cell destruction by its toxin domain.

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Authors and Affiliations

  1. Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran

    Fateme Sefid

  2. Department of Biology, Science and Art University, Yazd, Iran

    Fateme Sefid

  3. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Armina Alagheband Bahrami

  4. Department Medical Biochemistry and Biophysics, Division Medical Inflammation Research, Karolinska Institute, Stockholm, Sweden

    Zahra Payandeh

  5. Department of Biology Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran

    Saeed Khalili

  6. School of Mechanical Engineering, Yazd University, Yazd, Iran

    Ghasem Azamirad

  7. Reproductive & Genetic Unit, Research and Clinical Center for Infertility, Yazd Reproduction Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Seyed Mehdy Kalantar

  8. Department of Biology, Faculty of Science, Yazd University, Yazd, Iran

    Maryam Touhidinia

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  1. Fateme Sefid
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  2. Armina Alagheband Bahrami
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  3. Zahra Payandeh
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  4. Saeed Khalili
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Correspondence to Ghasem Azamirad or Seyed Mehdy Kalantar.

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Sefid, F., Alagheband Bahrami, A., Payandeh, Z. et al. Ofatumumab and Granzyme B as immunotoxin against CD20 antigen. In Silico Pharmacol. 10, 6 (2022). https://doi.org/10.1007/s40203-022-00120-6

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