Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics
Cancer therapeutics approved for clinical application include oncolytic viruses and antibodies, which evolved by nature, but were improved by molecular engineering. Both facilitate outstanding tumor selectivity and pleiotropic activities, but also face challenges, such as tumor heterogeneity and lim...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2021.1982447 |
| _version_ | 1811343665336942592 |
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| author | Roland E. Kontermann Guy Ungerechts Dirk M. Nettelbeck |
| author_facet | Roland E. Kontermann Guy Ungerechts Dirk M. Nettelbeck |
| author_sort | Roland E. Kontermann |
| collection | DOAJ |
| description | Cancer therapeutics approved for clinical application include oncolytic viruses and antibodies, which evolved by nature, but were improved by molecular engineering. Both facilitate outstanding tumor selectivity and pleiotropic activities, but also face challenges, such as tumor heterogeneity and limited tumor penetration. An innovative strategy to address these challenges combines both agents in a single, multitasking therapeutic, i.e., an oncolytic virus engineered to express therapeutic antibodies. Such viro-antibody therapies genetically deliver antibodies to tumors from amplified virus genomes, thereby complementing viral oncolysis with antibody-defined therapeutic action. Here, we review the strategies of viro-antibody therapy that have been pursued exploiting diverse virus platforms, antibody formats, and antibody-mediated modes of action. We provide a comprehensive overview of reported antibody-encoding oncolytic viruses and highlight the achievements of 13 years of viro-antibody research. It has been shown that functional therapeutic antibodies of different formats can be expressed in and released from cancer cells infected with different oncolytic viruses. Virus-encoded antibodies have implemented direct tumor cell killing, anti-angiogenesis, or activation of adaptive immune responses to kill tumor cells, tumor stroma cells or inhibitory immune cells. Importantly, numerous reports have shown therapeutic activity complementary to viral oncolysis for these modalities. Also, challenges for future research have been revealed. Established engineering technologies for both oncolytic viruses and antibodies will enable researchers to address these challenges, facilitating the development of effective viro-antibody therapeutics. |
| first_indexed | 2024-04-13T19:33:56Z |
| format | Article |
| id | doaj.art-efb7def1050c412b8a11a7aaf395721f |
| institution | Directory Open Access Journal |
| issn | 1942-0862 1942-0870 |
| language | English |
| last_indexed | 2024-04-13T19:33:56Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj.art-efb7def1050c412b8a11a7aaf395721f2022-12-22T02:33:07ZengTaylor & Francis GroupmAbs1942-08621942-08702021-01-0113110.1080/19420862.2021.1982447Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeuticsRoland E. Kontermann0Guy Ungerechts1Dirk M. Nettelbeck2Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, GermanyClinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Heidelberg, GermanyClinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Heidelberg, GermanyCancer therapeutics approved for clinical application include oncolytic viruses and antibodies, which evolved by nature, but were improved by molecular engineering. Both facilitate outstanding tumor selectivity and pleiotropic activities, but also face challenges, such as tumor heterogeneity and limited tumor penetration. An innovative strategy to address these challenges combines both agents in a single, multitasking therapeutic, i.e., an oncolytic virus engineered to express therapeutic antibodies. Such viro-antibody therapies genetically deliver antibodies to tumors from amplified virus genomes, thereby complementing viral oncolysis with antibody-defined therapeutic action. Here, we review the strategies of viro-antibody therapy that have been pursued exploiting diverse virus platforms, antibody formats, and antibody-mediated modes of action. We provide a comprehensive overview of reported antibody-encoding oncolytic viruses and highlight the achievements of 13 years of viro-antibody research. It has been shown that functional therapeutic antibodies of different formats can be expressed in and released from cancer cells infected with different oncolytic viruses. Virus-encoded antibodies have implemented direct tumor cell killing, anti-angiogenesis, or activation of adaptive immune responses to kill tumor cells, tumor stroma cells or inhibitory immune cells. Importantly, numerous reports have shown therapeutic activity complementary to viral oncolysis for these modalities. Also, challenges for future research have been revealed. Established engineering technologies for both oncolytic viruses and antibodies will enable researchers to address these challenges, facilitating the development of effective viro-antibody therapeutics.https://www.tandfonline.com/doi/10.1080/19420862.2021.1982447Oncolytic virustherapeutic antibodygene therapygenetic antibody deliveryvirus engineeringantibody engineering |
| spellingShingle | Roland E. Kontermann Guy Ungerechts Dirk M. Nettelbeck Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics mAbs Oncolytic virus therapeutic antibody gene therapy genetic antibody delivery virus engineering antibody engineering |
| title | Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics |
| title_full | Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics |
| title_fullStr | Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics |
| title_full_unstemmed | Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics |
| title_short | Viro-antibody therapy: engineering oncolytic viruses for genetic delivery of diverse antibody-based biotherapeutics |
| title_sort | viro antibody therapy engineering oncolytic viruses for genetic delivery of diverse antibody based biotherapeutics |
| topic | Oncolytic virus therapeutic antibody gene therapy genetic antibody delivery virus engineering antibody engineering |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2021.1982447 |
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