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Atezolizumab and granzyme B as immunotoxin against PD-L1 antigen; an insilico study

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Abstract

CD274 gene encodes programmed death-ligand 1 (PD-L1) protein, also known as B7 homolog 1 (B7-H1), which is a crucial hallmark for highly proliferation cells including cancer cells. PD-1 and PD-L1 interaction is assumed as a negative regulator for immune response which can inhibit the T cell growth and cytokine secretion and supports tumor cells evasion from immune system. therefore, PD-L1 could be assumed as a candidate target for immune-therapy. The predicted structure of PD-L1 indicates (Gly4Ser) 3 linker-based chains links. In that line, different simulation softwares applied to explore the structure of granzyme B (GrB), a serine protease in cytotoxic lymphocytes granules as an apoptosis mediator, was attached to its specific antibody structure (atezolizumab) via an adaptor sequence. Evaluation of accuracy, energy minimization and characterization of biological properties of the final processed structure were performed and our computational outcomes indicated that the employed method for structure prediction has been successfully managed to design the immunotoxin structure. It is necessary to mention that, 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 PD-L1 in an accurate orientation and initiates cancer cell destruction by its toxin domain.

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Availability of data and materials

Data presented in this manuscript is available upon request.

Abbreviations

PD-L1:

Programmed death-1

GrB:

Granzyme B

PDB:

Protein data bank

OPIG:

Oxford Protein Informatics Group

RMSD:

Root-mean-square deviation

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Acknowledgements

The authors wish to thank Immunology Research Center, Tabriz-Iran and Shahid Sadoughi University of Medical Science, Yazd, Iran for their support by unrestricted free access to the web site for data collection.

Funding

This work was financially supported by grants from the Iran National Science Foundation (INSF), Iran (project no. 97021150) and Tabriz University of Medical Sciences, Tabriz, Iran (project no. 61892). We gratefully acknowledge them for their contribution to this study.

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Authors and Affiliations

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

    Fateme Sefid & Seyed Mehdi Kalantar

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

    Fateme Sefid & Mahnam Alaei Ardakani

  3. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Zahra Payandeh & Behzad Baradaran

  4. Hospital of Xi’an Jiaotong University (Xibei Hospital), 710004 Xi’an, China

    Zahra Payandeh

  5. Department of Mechanical Engineering, Yazd University, Yazd, Iran

    Ghasem Azamirad

  6. Institute of Biochemistry and Biophysics, Tehran University, Tehran, Iran

    Mohsen Nabi Afjadi

  7. Dietary Supplements and Probiotic Research Center, Alborz University of Medical Science, Karaj, Iran

    Maryam Islami

  8. Department of Medical Biotechnology, Faculty of Medicine, Arak University of Medical Science, Arāk, Iran

    Maryam Darvish

  9. Research and Clinical Center for Infertility, Reproduction Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Seyed Mehdi Kalantar

  10. Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Houman Kahroba

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  1. Fateme Sefid
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  2. Zahra Payandeh
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  3. Ghasem Azamirad
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  6. Maryam Islami
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  8. Seyed Mehdi Kalantar
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  9. Houman Kahroba
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  10. Mahnam Alaei Ardakani
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All authors participated in writing. Writing-review and language correction.

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Correspondence to Ghasem Azamirad, Behzad Baradaran or Seyed Mehdi Kalantar.

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Sefid, F., Payandeh, Z., Azamirad, G. et al. Atezolizumab and granzyme B as immunotoxin against PD-L1 antigen; an insilico study. In Silico Pharmacol. 9, 20 (2021). https://doi.org/10.1007/s40203-021-00076-z

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