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Novel antigens for targeted radioimmunotherapy in hepatocellular carcinoma

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Abstract

Liver cancer is the sixth common cancer and forth cause of cancer-related death worldwide. Based on usually advanced stages of hepatocellular carcinoma (HCC) at the time of diagnosis, therapeutic options are limited and, in many cases, not effective, and typically result in the tumor recurrence with a poor prognosis. Radioimmunotherapy (RIT) offers a selective internal radiation therapy approach using beta or alpha emitting radionuclides conjugated with tumor-specific monoclonal antibodies (mAbs), or specific selective peptides. When compared to chemotherapy or radiotherapy, radiolabeled mAbs against cancer-associated antigens could provide a high therapeutic and exclusive radiation dose for cancerous cells while decreasing the exposure-induced side effects to healthy tissues. The recent advances in cancer immunotherapy, such as blockade of immune-checkpoint inhibitors (ICIs), has changed the landscape of cancer therapy, and the efficacy of different classes of immunotherapy has been tested in many clinical trials. Taking into account the use of ICIs in the liver tumor microenvironment, combined therapies with different approaches may enhance the outcome in the future clinical studies. With the development of novel immunotherapy treatment options in the recent years, there has been a great deal of information about combining the diverse treatment modalities to boost the effectiveness of immunomodulatory drugs. In this opinion review, we will discuss the recent advancements in RIT. The current status of immunotherapy and internal radiotherapy will be updated, and we will propose novel approaches for the combination of both techniques.

Graphical abstract

Potential target antigens for radioimmunotherapy in Hepatocellular carcinoma (HCC). HCC radioimmunotherapy target antigens are the most specific and commonly accessible antigens on the surface of HCC cells. CTLA-4 ligand and receptor, TAMs, PD-1/PD-L, TIM-3, specific IEXs/TEXs, ROBO1, and cluster of differentiation antigens CD105, CD147 could all be used in HCC radioimmunotherapy. Abbreviations: TAMs, tumor-associated macrophages; CTLA-4, cytotoxic T-lymphocyte associated antigen-4; PD-1, Programmed cell death protein 1; PD-L, programmed death-ligand1; TIM-3, T-cell immunoglobulin (Ig) and mucin-domain containing protein-3; IEXs, immune cell-derived exosomes; TEXs, tumor-derived exosomes.

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Acknowledgements

Authors would like to express their gratitude to their colleagues in Royan institute for their support.

Funding

The authors would like to thank the Royan Institute, Tehran, Iran, for supporting this study. The study was partly supported by “National Cancer Control Charity Foundation”, to MV, registration number 41476, Tehran, IRAN. AS and PT were supported by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare” (No 075-15-2020-926).

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  1. Mahsa Pourhamzeh and Samieh Asadian contributed equally to this paper.

Authors and Affiliations

  1. Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

    Mahsa Pourhamzeh, Samieh Asadian & Massoud Vosough

  2. Departments of Pathology and Medicine, UC San Diego, La Jolla, CA, USA

    Mahsa Pourhamzeh & Elahe Shahriari

  3. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran

    Hamed Mirzaei

  4. Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran

    Azita Minaei

  5. World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow, Russia

    Anastasia Shpichka & Peter Timashev

  6. Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, Russia

    Anastasia Shpichka & Peter Timashev

  7. Chemistry Department, Lomonosov Moscow State University, Moscow, Russia

    Anastasia Shpichka & Peter Timashev

  8. School of Biomedical Engineering, University of Technology Sydney, Sydney, 2007, Australia

    Hamidreza Aboulkheyr Es

  9. Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden

    Moustapha Hassan & Massoud Vosough

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  1. Mahsa Pourhamzeh
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Contributions

MP, SA, and MV outlined the manuscript. SA and MP drafted the manuscript with primary editing and revision support from HM, PM, AM, ES, AS, HAE, PT, MH, and MV. PT, MH, and MV critically revised the manuscript for all content and coordinated the manuscript preparation and submission. All authors read and approved the final version.

Corresponding authors

Correspondence to Peter Timashev or Massoud Vosough.

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Pourhamzeh, M., Asadian, S., Mirzaei, H. et al. Novel antigens for targeted radioimmunotherapy in hepatocellular carcinoma. Mol Cell Biochem 478, 23–37 (2023). https://doi.org/10.1007/s11010-022-04483-4

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