Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies

doi:10.1186/s40364-024-00617-6

Review

. 2024 Jul 29;12(1):71.

doi: 10.1186/s40364-024-00617-6.

Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies

Wei Zhang^{1

2}, Miao Zeng^{1

2}, Yisheng Li^{3

4}, Li Yu^{5

6}

Affiliations

¹ Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Hematology Institution of Shenzhen University, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518000, China.
² Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical school, Shenzhen, 518060, China.
³ Shenzhen Haoshi Biotechnology Co., Ltd, No. 155 Hongtian Road, Xinqiao Street, Bao'an District, Shenzhen, Guangdong, 518125, China.
⁴ Haoshi Cell Therapy Institute, Shenzhen University, Shenzhen, China.
⁵ Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Hematology Institution of Shenzhen University, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518000, China. yuli@szu.edu.cn.
⁶ Haoshi Cell Therapy Institute, Shenzhen University, Shenzhen, China. yuli@szu.edu.cn.

PMID: 39075601
PMCID: PMC11287861
DOI: 10.1186/s40364-024-00617-6

Review

Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies

Wei Zhang et al. Biomark Res. 2024.

. 2024 Jul 29;12(1):71.

doi: 10.1186/s40364-024-00617-6.

Authors

Wei Zhang^{1

2}, Miao Zeng^{1

2}, Yisheng Li^{3

4}, Li Yu^{5

6}

Affiliations

¹ Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Hematology Institution of Shenzhen University, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518000, China.
² Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical school, Shenzhen, 518060, China.
³ Shenzhen Haoshi Biotechnology Co., Ltd, No. 155 Hongtian Road, Xinqiao Street, Bao'an District, Shenzhen, Guangdong, 518125, China.
⁴ Haoshi Cell Therapy Institute, Shenzhen University, Shenzhen, China.
⁵ Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Hematology Institution of Shenzhen University, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518000, China. yuli@szu.edu.cn.
⁶ Haoshi Cell Therapy Institute, Shenzhen University, Shenzhen, China. yuli@szu.edu.cn.

PMID: 39075601
PMCID: PMC11287861
DOI: 10.1186/s40364-024-00617-6

Abstract

Adoptive cell therapies (ACTs) have revolutionized cancer immunotherapy, prompting exploration into their application against oncoviruses. Oncoviruses such as human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV) contribute significantly (12-25%) to human malignancies through direct or indirect oncogenic mechanisms. These viruses persistently or latently infect cells, disrupt cellular homeostasis and pathways, challenging current antiviral treatment paradigms. Moreover, viral infections pose additional risks in the setting of long-term cancer therapy and lead to morbidity and mortality. Virally encoded oncoproteins, which are tumor-restricted, immunologically foreign, and even uniformly expressed, represent promising targets for patient-tailored ACTs. This review elucidates the rationale for leveraging viral antigen-specific ACTs in combating viral-associated malignancies. On this basis, ongoing preclinical studies consolidate our understanding of harnessing ACTs against viral malignancies, underscoring their potential to eradicate viruses implicated in cancer progression. Furthermore, we scrutinize the current landscape of clinical trials focusing on virus-specific ACTs and discuss their implications for therapeutic advancement.

Keywords: Adoptive cell therapies (ACTs); Oncoprotein; Oncovirus; Viral antigen; Viral malignancy.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
a Viral persistent or latent infection and host cellular immunity against oncogenic infection (By Figdraw). A variety of virally oncogenic mechanisms determine the transformation and maintenance of the malignancy. Virus-infected cells can be recognized and eliminated by host cellular immunity. b Schematic diagram of ACTs on viral malignancies. Engineered TILs, DCs, CAR-T cells, TCR-T cells, and VST therapies have the potential for application to viral malignancies. CAR-T cells target the virally-encoded cell surface antigen through an antibody-based scFv. In contrast, TCR-T cells target a virus-derived peptide on MHC complex. In TIL therapy, tumor is surgically resected and T-cells are expanded from the tumor ex vivo. TILs target viral antigens as well as non-viral proteins. The VST therapy aims to enhance the host immune system’s ability to clear infected cells by using activated virus specific T-cells. While the DCs enable to induce and amplify virus-specific CTLs.

**Fig. 2**
Virally encoded antigens and relevant utilization of oncovirus-specific ACTs in viral malignancies. a HPV-specific ACTs. b HBV-specific ACTs. c HCV-specific ACTs. d CMV-specific ACTs. e EBV-specific ACTs. f HIV-1-specific ACTs.

See this image and copyright information in PMC

References

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[1] Tayyar R, Ho D. Herpes Simplex Virus and Varicella Zoster Virus infections in Cancer patients. Viruses. 2023;15(2). - PMC - PubMed

[2] Tayyar R, Ho D. Herpes Simplex Virus and Varicella Zoster Virus infections in Cancer patients. Viruses. 2023;15(2). - PMC - PubMed

[3] Jankovic M, Knezevic T, Tomic A, Milicevic O, Jovanovic T, Djunic I et al. Human cytomegalovirus oncoprotection across diverse populations, Tumor histologies, and Age groups: the relevance for prospective Vaccinal Therapy. Int J Mol Sci. 2024;25(7). - PMC - PubMed

[4] Jankovic M, Knezevic T, Tomic A, Milicevic O, Jovanovic T, Djunic I et al. Human cytomegalovirus oncoprotection across diverse populations, Tumor histologies, and Age groups: the relevance for prospective Vaccinal Therapy. Int J Mol Sci. 2024;25(7). - PMC - PubMed

[5] Guyon J, Haidar Ahmad S, El Baba R, Le Quang M, Bikfalvi A, Daubon T et al. Generation of glioblastoma in mice engrafted with human cytomegalovirus-infected astrocytes. Cancer Gene Ther. 2024. - PMC - PubMed

[6] Guyon J, Haidar Ahmad S, El Baba R, Le Quang M, Bikfalvi A, Daubon T et al. Generation of glioblastoma in mice engrafted with human cytomegalovirus-infected astrocytes. Cancer Gene Ther. 2024. - PMC - PubMed

[7] El Baba R, Pasquereau S, Haidar Ahmad S, Monnien F, Abad M, Bibeau F, et al. EZH2-Myc driven glioblastoma elicited by cytomegalovirus infection of human astrocytes. Oncogene. 2023;42(24):2031–45. 10.1038/s41388-023-02709-3 - DOI - PMC - PubMed

[8] El Baba R, Pasquereau S, Haidar Ahmad S, Monnien F, Abad M, Bibeau F, et al. EZH2-Myc driven glioblastoma elicited by cytomegalovirus infection of human astrocytes. Oncogene. 2023;42(24):2031–45. 10.1038/s41388-023-02709-3 - DOI - PMC - PubMed

[9] Nehme Z, Pasquereau S, Haidar Ahmad S, El Baba R, Herbein G. Polyploid giant cancer cells, EZH2 and myc upregulation in mammary epithelial cells infected with high-risk human cytomegalovirus. EBioMedicine. 2022;80:104056. 10.1016/j.ebiom.2022.104056 - DOI - PMC - PubMed

[10] Nehme Z, Pasquereau S, Haidar Ahmad S, El Baba R, Herbein G. Polyploid giant cancer cells, EZH2 and myc upregulation in mammary epithelial cells infected with high-risk human cytomegalovirus. EBioMedicine. 2022;80:104056. 10.1016/j.ebiom.2022.104056 - DOI - PMC - PubMed

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Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies

Affiliations

Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies

Authors

Affiliations

Abstract

Conflict of interest statement

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