Liposomal oncolytic adenovirus as a neoadjuvant therapy for triple-negative breast cancer
Abstract Breast cancer remains one of the leading causes of cancer-related death, with triple-negative breast cancer (TNBC) accounting for 15–20% of cases. TNBC, characterized by the absence of ER, PR, and HER2 protein, is an aggressive form of breast cancer that is unresponsive to hormonal therapie...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-00211-2 |
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| author | Jaimin R. Shah Tao Dong Abraham T. Phung Sohini Khan Omonigho Aisagbonhi Sarah L. Blair Michael Bouvet William C. Trogler Andrew C. Kummel |
| author_facet | Jaimin R. Shah Tao Dong Abraham T. Phung Sohini Khan Omonigho Aisagbonhi Sarah L. Blair Michael Bouvet William C. Trogler Andrew C. Kummel |
| author_sort | Jaimin R. Shah |
| collection | DOAJ |
| description | Abstract Breast cancer remains one of the leading causes of cancer-related death, with triple-negative breast cancer (TNBC) accounting for 15–20% of cases. TNBC, characterized by the absence of ER, PR, and HER2 protein, is an aggressive form of breast cancer that is unresponsive to hormonal therapies and HER2-targeted treatments, with fewer treatment options and poorer prognosis. Oncolytic adenoviruses (Ad) are a potential treatment option for TNBC but require coxsackievirus and adenovirus receptors (CAR) to effectively enter and transduce cancer cells. This study investigates a novel neoadjuvant therapy to improve the efficacy of an oncolytic Ad with human telomerase reverse transcriptase (Ad-hTERT) in CAR-low TNBC tumors using folate surface-modified liposomes to enhance delivery. This therapy helps deescalate treatment by reducing or eliminating the need for checkpoint inhibitors or toxic chemotherapy combinations. In vitro studies using CAR-low TNBC murine 4T1-eGFP cells, CAR-high TNBC human MDA-MB-231-GFP cells and several other TNBC human cancer cell lines with varying CAR expression demonstrated significantly higher cytotoxicity with encapsulated Ad-hTERT compared to Ad-hTERT. Similar results were observed in patient-derived primary TNBC cells. In vivo studies in immunocompetent mice with CAR-low 4T1-eGFP tumors revealed that encapsulated Ad-hTERT, administered as neoadjuvant therapy, resulted in stable or reduced tumor sizes, improved survival rates, higher apoptosis of cancer cells, lower cancer cell proliferation, and increased T-cell infiltration in resected tumors. Furthermore, encapsulated Ad-hTERT prevented lung metastasis and tumor recurrence at the primary site, resulting in higher survival rates in mice. Thus, liposomal encapsulation of Ad may be a viable strategy for treating TNBC. |
| format | Article |
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| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-d4030a2d09f64729b0885b4b54bc8a812025-08-20T01:51:29ZengNature PortfolioScientific Reports2045-23222025-05-0115111810.1038/s41598-025-00211-2Liposomal oncolytic adenovirus as a neoadjuvant therapy for triple-negative breast cancerJaimin R. Shah0Tao Dong1Abraham T. Phung2Sohini Khan3Omonigho Aisagbonhi4Sarah L. Blair5Michael Bouvet6William C. Trogler7Andrew C. Kummel8Moores Cancer Center, University of California San DiegoMoores Cancer Center, University of California San DiegoMoores Cancer Center, University of California San DiegoMoores Cancer Center, University of California San DiegoMoores Cancer Center, University of California San DiegoMoores Cancer Center, University of California San DiegoMoores Cancer Center, University of California San DiegoDepartment of Chemistry & Biochemistry, University of California San DiegoMoores Cancer Center, University of California San DiegoAbstract Breast cancer remains one of the leading causes of cancer-related death, with triple-negative breast cancer (TNBC) accounting for 15–20% of cases. TNBC, characterized by the absence of ER, PR, and HER2 protein, is an aggressive form of breast cancer that is unresponsive to hormonal therapies and HER2-targeted treatments, with fewer treatment options and poorer prognosis. Oncolytic adenoviruses (Ad) are a potential treatment option for TNBC but require coxsackievirus and adenovirus receptors (CAR) to effectively enter and transduce cancer cells. This study investigates a novel neoadjuvant therapy to improve the efficacy of an oncolytic Ad with human telomerase reverse transcriptase (Ad-hTERT) in CAR-low TNBC tumors using folate surface-modified liposomes to enhance delivery. This therapy helps deescalate treatment by reducing or eliminating the need for checkpoint inhibitors or toxic chemotherapy combinations. In vitro studies using CAR-low TNBC murine 4T1-eGFP cells, CAR-high TNBC human MDA-MB-231-GFP cells and several other TNBC human cancer cell lines with varying CAR expression demonstrated significantly higher cytotoxicity with encapsulated Ad-hTERT compared to Ad-hTERT. Similar results were observed in patient-derived primary TNBC cells. In vivo studies in immunocompetent mice with CAR-low 4T1-eGFP tumors revealed that encapsulated Ad-hTERT, administered as neoadjuvant therapy, resulted in stable or reduced tumor sizes, improved survival rates, higher apoptosis of cancer cells, lower cancer cell proliferation, and increased T-cell infiltration in resected tumors. Furthermore, encapsulated Ad-hTERT prevented lung metastasis and tumor recurrence at the primary site, resulting in higher survival rates in mice. Thus, liposomal encapsulation of Ad may be a viable strategy for treating TNBC.https://doi.org/10.1038/s41598-025-00211-2Triple-negative breast cancerNeoadjuvant therapyOncolytic adenovirusCoxsackievirus and adenovirus receptorLiposomesMetastasis |
| spellingShingle | Jaimin R. Shah Tao Dong Abraham T. Phung Sohini Khan Omonigho Aisagbonhi Sarah L. Blair Michael Bouvet William C. Trogler Andrew C. Kummel Liposomal oncolytic adenovirus as a neoadjuvant therapy for triple-negative breast cancer Scientific Reports Triple-negative breast cancer Neoadjuvant therapy Oncolytic adenovirus Coxsackievirus and adenovirus receptor Liposomes Metastasis |
| title | Liposomal oncolytic adenovirus as a neoadjuvant therapy for triple-negative breast cancer |
| title_full | Liposomal oncolytic adenovirus as a neoadjuvant therapy for triple-negative breast cancer |
| title_fullStr | Liposomal oncolytic adenovirus as a neoadjuvant therapy for triple-negative breast cancer |
| title_full_unstemmed | Liposomal oncolytic adenovirus as a neoadjuvant therapy for triple-negative breast cancer |
| title_short | Liposomal oncolytic adenovirus as a neoadjuvant therapy for triple-negative breast cancer |
| title_sort | liposomal oncolytic adenovirus as a neoadjuvant therapy for triple negative breast cancer |
| topic | Triple-negative breast cancer Neoadjuvant therapy Oncolytic adenovirus Coxsackievirus and adenovirus receptor Liposomes Metastasis |
| url | https://doi.org/10.1038/s41598-025-00211-2 |
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