HydrAd: A Helper-Dependent Adenovirus Targeting Multiple Immune Pathways for Cancer Immunotherapy
For decades, Adenoviruses (Ads) have been staple cancer gene therapy vectors. Ads are highly immunogenic, making them effective adjuvants. These viruses have well characterized genomes, allowing for substantial modifications including capsid chimerism and therapeutic transgene insertion. Multiple ge...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/11/2769 |
| _version_ | 1797493872986685440 |
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| author | Amanda Rosewell Shaw Caroline Porter Greyson Biegert Lisa Jatta Masataka Suzuki |
| author_facet | Amanda Rosewell Shaw Caroline Porter Greyson Biegert Lisa Jatta Masataka Suzuki |
| author_sort | Amanda Rosewell Shaw |
| collection | DOAJ |
| description | For decades, Adenoviruses (Ads) have been staple cancer gene therapy vectors. Ads are highly immunogenic, making them effective adjuvants. These viruses have well characterized genomes, allowing for substantial modifications including capsid chimerism and therapeutic transgene insertion. Multiple generations of Ad vectors have been generated with reduced or enhanced immunogenicity, depending on their intended purpose, and with increased transgene capacity. The latest-generation Ad vector is the Helper-dependent Ad (HDAd), in which all viral coding sequences are removed from the genome, leaving only the cis-acting ITRs and packaging sequences, providing up to 34 kb of transgene capacity. Although HDAds are replication incompetent, their innate immunogenicity remains intact. Therefore, the HDAd is an ideal cancer gene therapy vector as its infection results in anti-viral immune stimulation that can be enhanced or redirected towards the tumor via transgene expression. Co-infection of tumor cells with an oncolytic Ad and an HDAd results in tumor cell lysis and amplification of HDAd-encoded transgene expression. Here, we describe an HDAd-based cancer gene therapy expressing multiple classes of immunomodulatory molecules to simultaneously stimulate multiple axes of immune pathways: the HydrAd. Overall, the HydrAd platform represents a promising cancer immunotherapy agent against complex solid tumors. |
| first_indexed | 2024-03-10T01:26:13Z |
| format | Article |
| id | doaj.art-c00c5fa258a94c68b67c51d7fc5f3b26 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T01:26:13Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c00c5fa258a94c68b67c51d7fc5f3b262023-11-23T13:50:51ZengMDPI AGCancers2072-66942022-06-011411276910.3390/cancers14112769HydrAd: A Helper-Dependent Adenovirus Targeting Multiple Immune Pathways for Cancer ImmunotherapyAmanda Rosewell Shaw0Caroline Porter1Greyson Biegert2Lisa Jatta3Masataka Suzuki4Department of Medicine, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Medicine, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Medicine, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Medicine, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Medicine, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX 77030, USAFor decades, Adenoviruses (Ads) have been staple cancer gene therapy vectors. Ads are highly immunogenic, making them effective adjuvants. These viruses have well characterized genomes, allowing for substantial modifications including capsid chimerism and therapeutic transgene insertion. Multiple generations of Ad vectors have been generated with reduced or enhanced immunogenicity, depending on their intended purpose, and with increased transgene capacity. The latest-generation Ad vector is the Helper-dependent Ad (HDAd), in which all viral coding sequences are removed from the genome, leaving only the cis-acting ITRs and packaging sequences, providing up to 34 kb of transgene capacity. Although HDAds are replication incompetent, their innate immunogenicity remains intact. Therefore, the HDAd is an ideal cancer gene therapy vector as its infection results in anti-viral immune stimulation that can be enhanced or redirected towards the tumor via transgene expression. Co-infection of tumor cells with an oncolytic Ad and an HDAd results in tumor cell lysis and amplification of HDAd-encoded transgene expression. Here, we describe an HDAd-based cancer gene therapy expressing multiple classes of immunomodulatory molecules to simultaneously stimulate multiple axes of immune pathways: the HydrAd. Overall, the HydrAd platform represents a promising cancer immunotherapy agent against complex solid tumors.https://www.mdpi.com/2072-6694/14/11/2769cancer immunotherapyoncolytic adenovirushelper-dependent adenoviruscancer gene therapy |
| spellingShingle | Amanda Rosewell Shaw Caroline Porter Greyson Biegert Lisa Jatta Masataka Suzuki HydrAd: A Helper-Dependent Adenovirus Targeting Multiple Immune Pathways for Cancer Immunotherapy Cancers cancer immunotherapy oncolytic adenovirus helper-dependent adenovirus cancer gene therapy |
| title | HydrAd: A Helper-Dependent Adenovirus Targeting Multiple Immune Pathways for Cancer Immunotherapy |
| title_full | HydrAd: A Helper-Dependent Adenovirus Targeting Multiple Immune Pathways for Cancer Immunotherapy |
| title_fullStr | HydrAd: A Helper-Dependent Adenovirus Targeting Multiple Immune Pathways for Cancer Immunotherapy |
| title_full_unstemmed | HydrAd: A Helper-Dependent Adenovirus Targeting Multiple Immune Pathways for Cancer Immunotherapy |
| title_short | HydrAd: A Helper-Dependent Adenovirus Targeting Multiple Immune Pathways for Cancer Immunotherapy |
| title_sort | hydrad a helper dependent adenovirus targeting multiple immune pathways for cancer immunotherapy |
| topic | cancer immunotherapy oncolytic adenovirus helper-dependent adenovirus cancer gene therapy |
| url | https://www.mdpi.com/2072-6694/14/11/2769 |
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