Cancer gene therapy最新文献_第8页

Intraperitoneal administration of adeno-associated virus encoding microRNA-29b for the treatment of peritoneal metastasis 腹膜内注射编码 microRNA-29b 的腺相关病毒治疗腹膜转移瘤。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-10-10 DOI: 10.1038/s41417-024-00837-w

Yuki Kaneko, Hideyuki Ohzawa, Yuki Kimura, Rei Takahashi, Misaki Matsumiya, Kohei Tamura, Yurie Futoh, Hideyo Miyato, Shin Saito, Hironori Yamaguchi, Yoshinori Hosoya, Ryota Watano, Hiroaki Mizukami, Naohiro Sata, Joji Kitayama

{"title":"Intraperitoneal administration of adeno-associated virus encoding microRNA-29b for the treatment of peritoneal metastasis","authors":"Yuki Kaneko, Hideyuki Ohzawa, Yuki Kimura, Rei Takahashi, Misaki Matsumiya, Kohei Tamura, Yurie Futoh, Hideyo Miyato, Shin Saito, Hironori Yamaguchi, Yoshinori Hosoya, Ryota Watano, Hiroaki Mizukami, Naohiro Sata, Joji Kitayama","doi":"10.1038/s41417-024-00837-w","DOIUrl":"10.1038/s41417-024-00837-w","url":null,"abstract":"This study explores a novel therapeutic approach for peritoneal metastasis (PM) using AAV-mediated delivery of tumor suppressor microRNA-29b (miR-29b) to peritoneal mesothelial cells (PMC). AAV serotypes 2 and DJ demonstrate high transduction efficiency for human and murine PMC, respectively. In vitro analysis indicates that AAV vectors encoding miR-29b precursor successfully elevate miR-29b expression in PMC and their secreted small extracellular vesicle (sEV), thereby inhibiting mesothelial mesenchymal transition and reducing subsequent attachment of tumor cells. A single intraperitoneal (IP) administration of AAV-DJ-miR-29b demonstrates robust and sustained transgene expression, suppressing peritoneal fibrosis and inhibiting the development of PM from gastric and pancreatic cancers. Additionally, AAV-DJ-miR-29b enhances the efficacy of IP chemotherapy using paclitaxel, restraining the growth of established PM. While conventional gene therapy for cancer encounters challenges targeting tumor cells directly but delivering miRNA to the tumor stroma offers a straightforward and efficient means of altering the microenvironment, leading to substantial inhibition of tumor growth. AAV-mediated miR-29b delivery to peritoneum via IP route presents a simple, minimally invasive, and promising therapeutic strategy for refractory PM.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 12","pages":"1818-1830"},"PeriodicalIF":4.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AAV-mediated combination gene therapy of inducible Caspase 9 and miR-199a-5p is therapeutic in hepatocellular carcinoma AAV介导的诱导型Caspase 9和miR-199a-5p联合基因疗法可治疗肝细胞癌。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-10-09 DOI: 10.1038/s41417-024-00844-x

Subhajit Pathak, Vijayata Singh, Narendra Kumar G., Giridhara R. Jayandharan

{"title":"AAV-mediated combination gene therapy of inducible Caspase 9 and miR-199a-5p is therapeutic in hepatocellular carcinoma","authors":"Subhajit Pathak, Vijayata Singh, Narendra Kumar G., Giridhara R. Jayandharan","doi":"10.1038/s41417-024-00844-x","DOIUrl":"10.1038/s41417-024-00844-x","url":null,"abstract":"Advanced-stage hepatocellular carcinoma (HCC) remains an untreatable disease with an overall survival of less than one year. One of the critical molecular mediators contributing to increased resistance to therapy and relapse, is increased hypoxia-inducible factor 1α (HIF-1α) levels, leading to metastasis of tumor cells. Several microRNAs are known to be dysregulated and impact HIF-1α expression in HCC. An in silico analysis demonstrated that hsa-miR-199a-5p is downregulated at various stages of HCC and is known to repress HIF-1α expression. Based on this analysis, we developed a combinatorial suicide gene therapy by employing hepatotropic Adeno-associated virus-based vectors encoding an inducible caspase 9 (iCasp9) and miR-199a. The overexpression of miR-199a-5p alone significantly decreased ( ~ 2-fold vs. Mock treated cells, p < 0.05) HIF-1α mRNA levels, with a concomitant increase in cancer cell cytotoxicity in Huh7 cells in vitro and in xenograft models in vivo. To further enhance the efficacy of gene therapy, we evaluated the synergistic therapeutic effect of AAV8-miR-199a and AAV6-iCasp9 in a xenograft model of HCC. Our data revealed that mice receiving combination suicide gene therapy exhibited reduced expression of HIF-1α ( ~ 4-fold vs. Mock, p < 0.001), with a significant reduction in tumor growth when compared to mock-treated animals. These findings underscore the therapeutic potential of downregulating HIF-1α during suicide gene therapy for HCC.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 12","pages":"1796-1803"},"PeriodicalIF":4.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systemic delivery of tannic acid-ferric-masked oncolytic adenovirus reprograms tumor microenvironment for improved therapeutic efficacy in glioblastoma 单宁酸-铁掩蔽的溶瘤腺病毒的全身给药可重塑肿瘤微环境，提高胶质母细胞瘤的疗效。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-10-09 DOI: 10.1038/s41417-024-00839-8

Guoqing Wang, Min Mu, Zongliang Zhang, Yongdong Chen, Nian Yang, Kunhong Zhong, Yanfang Li, Fang Lu, Gang Guo, Aiping Tong

{"title":"Systemic delivery of tannic acid-ferric-masked oncolytic adenovirus reprograms tumor microenvironment for improved therapeutic efficacy in glioblastoma","authors":"Guoqing Wang, Min Mu, Zongliang Zhang, Yongdong Chen, Nian Yang, Kunhong Zhong, Yanfang Li, Fang Lu, Gang Guo, Aiping Tong","doi":"10.1038/s41417-024-00839-8","DOIUrl":"10.1038/s41417-024-00839-8","url":null,"abstract":"Glioblastoma (GBM) represents the most aggressive primary brain tumor, and urgently requires effective treatments. Oncolytic adenovirus (OA) shows promise as a potential candidate for clinical antitumor therapy, including in the treatment of GBM. Nevertheless, the systemic delivery of OA continues to face challenges, leading to significantly compromised antitumor efficacy. In this study, we developed an innovative approach by encapsulating CXCL11-armed OA with tannic acid and Fe3+ (TA-Fe3+) to realize the systemic delivery of OA. The nanocarrier’s ability to protect the OA from elimination by host immune response was evaluated in vitro and in vivo. We evaluated the antitumor effect and safety profile of OA@TA-Fe3+ in a GBM-bearing mice model. OA@TA-Fe3+ effectively safeguarded the virus from host immune clearance and extended its circulation in vivo. After targeting tumor sites, TA-Fe3+ could dissolve and release Fe3+ and OA. Fe3+-induced O2 production from H2O2 relieved the hypoxic state, and promoted OA replication, leading to a remarkable alteration of tumor immune microenvironment and enhancement in antitumor efficacy. Moreover, the systemic delivery of OA@TA-Fe3+ was safe without inflammation or organ damage. Our findings demonstrated the promising potential of systemically delivering the engineered OA for effective oncolytic virotherapy against GBM.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 12","pages":"1-14"},"PeriodicalIF":4.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: PARD6A promotes lung adenocarcinoma cell proliferation and invasion through Serpina3 更正：PARD6A 通过 Serpina3 促进肺腺癌细胞增殖和侵袭。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-10-08 DOI: 10.1038/s41417-024-00840-1

Lanlin Hu, Mingxin Liu, Bo Tang, Xurui Li, Huasheng Xu, Huani Wang, Dandan Wang, Sijia Liu, Chuan Xu

引用次数: 0

AMIGO2 enhances the invasive potential of colorectal cancer by inducing EMT AMIGO2 通过诱导 EMT 增强结直肠癌的侵袭潜力。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-10-08 DOI: 10.1038/s41417-024-00842-z

Runa Izutsu, Mitsuhiko Osaki, HeeKyung Seong, Sanami Ogata, Reo Sato, Jun-ichi Hamada, Futoshi Okada

{"title":"AMIGO2 enhances the invasive potential of colorectal cancer by inducing EMT","authors":"Runa Izutsu, Mitsuhiko Osaki, HeeKyung Seong, Sanami Ogata, Reo Sato, Jun-ichi Hamada, Futoshi Okada","doi":"10.1038/s41417-024-00842-z","DOIUrl":"10.1038/s41417-024-00842-z","url":null,"abstract":"In our previous studies, we identified amphoterin-inducible gene and open reading frame 2 (AMIGO2) as a driver gene for liver metastasis and found that AMIGO2 expression in cancer cells worsens the prognosis of patients with colorectal cancer (CRC). Epithelial–mesenchymal transition (EMT) is a trigger for CRC to acquire a malignant phenotype, such as invasive potential, leading to metastasis. However, the role of AMIGO2 expression in the invasive potential of CRC cells remains unclear. Thus, this study aimed to examine AMIGO2 expression and elucidate the mechanisms by which it induces EMT and promotes CRC invasion. Activation of the TGFβ/Smad signaling pathway was found involved in AMIGO2-induced EMT, and treatment with the TGFβ receptor inhibitor LY2109761 suppressed AMIGO2-induced EMT. Studies using CRC samples showed that AMIGO2 expression was highly upregulated in the invasive front, where AMIGO2 expression was localized to the nucleus and associated with EMT marker expression. These results suggest that the nuclear translocation of AMIGO2 induces EMT to promote CRC invasion by activating the TGFβ/Smad signaling pathway. Thus, AMIGO2 is an attractive therapeutic target for inhibiting EMT and metastatic CRC progression.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 12","pages":"1786-1795"},"PeriodicalIF":4.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting CREB-binding protein (CBP) abrogates colorectal cancer stemness through epigenetic regulation of C-MYC 靶向 CREB 结合蛋白（CBP）可通过对 C-MYC 的表观遗传调控来削弱结直肠癌干性。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-10-02 DOI: 10.1038/s41417-024-00838-9

Dai-Jung Chung, Chun-Hao Wang, Pin‑Jung Liu, Shang-Kok Ng, Cong-Kai Luo, Si-Han Jwo, Chin-Tzu Li, Dai-Yi Hsu, Chia-Chu Fan, Tzu-Tang Wei

{"title":"Targeting CREB-binding protein (CBP) abrogates colorectal cancer stemness through epigenetic regulation of C-MYC","authors":"Dai-Jung Chung, Chun-Hao Wang, Pin‑Jung Liu, Shang-Kok Ng, Cong-Kai Luo, Si-Han Jwo, Chin-Tzu Li, Dai-Yi Hsu, Chia-Chu Fan, Tzu-Tang Wei","doi":"10.1038/s41417-024-00838-9","DOIUrl":"10.1038/s41417-024-00838-9","url":null,"abstract":"Colorectal cancer (CRC) is a common cancer worldwide with an increasing annual incidence. Cancer stem cells (CSCs) play important roles in the occurrence, development, recurrence, and metastasis of CRC. The molecular mechanism regulating the development of colorectal CSCs remains unclear. The discovery of human induced pluripotent stem cells (hiPSCs) through somatic cell reprogramming has revolutionized the fields of stem cell biology and translational medicine. In the present study, we converted hiPSCs into cancer stem-like cells by culture with conditioned medium (CM) from CRC cells. These transformed cells, termed hiPSC-CSCs, displayed cancer stem-like properties, including a spheroid morphology and the expression of both pluripotency and CSC markers. HiPSC-CSCs showed tumorigenic and metastatic abilities in mouse models. The epithelial-mesenchymal transition phenotype was observed in hiPSC-CSCs, which promoted their migration and angiogenesis. Interestingly, upregulation of C-MYC was observed during the differentiation of hiPSC-CSCs. Mechanistically, CREB binding protein (CBP) bound to the C-MYC promoter, while histone deacetylase 1 and 3 (HDAC1/3) dissociated from the promoter, ultimately leading to an increase in histone acetylation and C-MYC transcriptional activation during the differentiation of hiPSC-CSCs. Pharmacological treatment with a CBP inhibitor or abrogation of CBP expression with a CRISPR/Cas9-based strategy reduced the stemness of hiPSC-CSCs. This study demonstrates for the first time that colorectal CSCs can be generated from hiPSCs. The upregulation of C-MYC via histone acetylation plays a crucial role during the conversion process. Inhibition of CBP is a potential strategy for attenuating the stemness of colorectal CSCs.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 11","pages":"1734-1748"},"PeriodicalIF":4.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microbiota in tumors: new factor influencing cancer development 肿瘤中的微生物群：影响癌症发展的新因素。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-09-28 DOI: 10.1038/s41417-024-00833-0

Haixia Jiang, Lan Li, Yunxia Bao, Xiongyue Cao, Lifang Ma

{"title":"Microbiota in tumors: new factor influencing cancer development","authors":"Haixia Jiang, Lan Li, Yunxia Bao, Xiongyue Cao, Lifang Ma","doi":"10.1038/s41417-024-00833-0","DOIUrl":"10.1038/s41417-024-00833-0","url":null,"abstract":"Tumor microbiota research is a new field in oncology. With the advancement of high-throughput sequencing, there is growing evidence that a microbial community exists within tumor tissue. How these bacteria access tumor cells varies, including through the invasion of mucous membranes, the bloodstream, or the gut-organ axis. Previous literature has shown that microbes promote the development and progression of cancer through various mechanisms, such as affecting the host’s immune system, promoting inflammation, regulating metabolism, and activating invasion and transfer. The study of the tumor microbiota offers a new perspective for the diagnosis and treatment of cancer, and it holds the potential for the development of new diagnostic tools and therapies. The role of the tumor microbiota in the pathogenesis of cancer is becoming increasingly evident, and future research will continue to uncover the specific mechanisms of action of these microbes, potentially shedding light on new strategies and methods for cancer prevention and therapy. This article reviews the latest advancements in this field, including how intratumor microbes migrate, their carcinogenic mechanisms, and the characteristics of different types of tumor microbes as well as the application of relevant methods in tumor microbiota research and the clinical values of targeting tumor microbes in cancer therapy.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 12","pages":"1773-1785"},"PeriodicalIF":4.8,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00833-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging roles of bases modifications and DNA repair proteins in onco-miRNA processing: novel insights in cancer biology 碱基修饰和 DNA 修复蛋白在 onco-miRNA 处理中的新作用：癌症生物学的新见解。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-09-25 DOI: 10.1038/s41417-024-00836-x

Giovanna Mangiapane, Vito Giuseppe D’Agostino, Gianluca Tell

{"title":"Emerging roles of bases modifications and DNA repair proteins in onco-miRNA processing: novel insights in cancer biology","authors":"Giovanna Mangiapane, Vito Giuseppe D’Agostino, Gianluca Tell","doi":"10.1038/s41417-024-00836-x","DOIUrl":"10.1038/s41417-024-00836-x","url":null,"abstract":"Onco-microRNAs (onco-miRNAs) are essential players in the post-transcriptional regulation of gene expression and exert a crucial role in tumorigenesis. Novel information about the epitranscriptomic modifications, involved in onco-miRNAs biogenesis, and in the modulation of their interplay with regulatory factors responsible for their processing and sorting are emerging. In this review, we highlight the contribution of bases modifications, sequence motifs, and secondary structures on miRNAs processing and sorting. We focus on several modes of action of RNA binding proteins (RBPs) on these processes. Moreover, we describe the new emerging scenario that shows an unexpected though essential role of selected DNA repair proteins in actively participating in these events, highlighting the original intervention represented by the non-canonical functions of Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), a central player in Base Excision Repair (BER) pathway of DNA lesions. Taking advantage of this new knowledge will help in prospecting new cancer diagnostic and therapeutic strategies.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 12","pages":"1765-1772"},"PeriodicalIF":4.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00836-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multifaceted role of microRNA-301a in human cancer: from biomarker potential to therapeutic targeting microRNA-301a 在人类癌症中的多方面作用：从生物标记物潜力到治疗靶点。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-09-24 DOI: 10.1038/s41417-024-00832-1

Yuhang Chen, Chien-Shan Cheng, Lianyu Chen

{"title":"Multifaceted role of microRNA-301a in human cancer: from biomarker potential to therapeutic targeting","authors":"Yuhang Chen, Chien-Shan Cheng, Lianyu Chen","doi":"10.1038/s41417-024-00832-1","DOIUrl":"10.1038/s41417-024-00832-1","url":null,"abstract":"With the growing data on microRNA (miRNA) expression in tissues and circulation, there is increasing evidence for the potential of microRNAs to serve as biomarkers in cancer diagnosis and prognosis, as well as novel therapeutic targets. The expression level of miRNA-301a (miR-301a) is altered in a wide range of human tumor types, and numerous studies have revealed the roles of miR-301a in tumorigenesis and tumor progression. Herein, we comprehensively summarize, compare, and contrast the research advancements on the role of miR-301a in different cancers. Differential expression patterns of miR-301a in tissues and biofluids are implicated in cancer diagnosis, treatment response, and prognosis. MiR-301a modulates the expression of multiple genes, other noncoding RNAs, and signaling cascade via direct or indirect regulation in human cancer proliferation, migration, invasion, angiogenesis, and radio- or chemotherapy resistance. Cancer cell-associated miR-301a affects the tumor microenvironment through the alteration of immune function and cancer metabolism. These findings highlight the functional roles, clinical implications, and therapeutic relevance of miR-301a in various human cancers.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 12","pages":"1754-1764"},"PeriodicalIF":4.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extracellular vesicle-based anti-HOXB7 CD8+ T cell-specific vaccination strengthens antitumor effects induced by vaccination against Her2/neu 基于细胞外囊泡的抗HOXB7 CD8+ T细胞特异性疫苗接种可加强Her2/neu疫苗接种的抗肿瘤效果。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-09-19 DOI: 10.1038/s41417-024-00831-2

Flavia Ferrantelli, Francesco Manfredi, Micaela Donnini, Patrizia Leone, Katherina Pugliese, Eleonora Olivetta, Andrea Giovannelli, Antonio Di Virgilio, Maurizio Federico, Chiara Chiozzini

{"title":"Extracellular vesicle-based anti-HOXB7 CD8+ T cell-specific vaccination strengthens antitumor effects induced by vaccination against Her2/neu","authors":"Flavia Ferrantelli, Francesco Manfredi, Micaela Donnini, Patrizia Leone, Katherina Pugliese, Eleonora Olivetta, Andrea Giovannelli, Antonio Di Virgilio, Maurizio Federico, Chiara Chiozzini","doi":"10.1038/s41417-024-00831-2","DOIUrl":"10.1038/s41417-024-00831-2","url":null,"abstract":"We previously developed an innovative strategy to induce CD8+ T lymphocyte-immunity through in vivo engineering of extracellular vesicles (EVs). This approach relies on intramuscular injection of DNA expressing antigens of interest fused at a biologically-inactive HIV-1 Nef protein mutant (Nefmut). Nefmut is very efficiently incorporated into EVs, thus conveying large amounts of fusion proteins into EVs released by transfected cells. This platform proved successful against highly immunogenic tumor-specific antigens. Here, we tested whether antigen-specific CD8+ T cell immune responses induced by engineered EVs can counteract the growth of tumors expressing two “self” tumor-associated antigens (TAAs): HOXB7 and Her2/neu. FVB/N mice were injected with DNA vectors expressing Nefmut fused to HOXB7 or Her2/neu, singly and in combination, before subcutaneous implantation of breast carcinoma cells co-expressing HOXB7 and Her2/neu. All mice immunized with the combination vaccine remained tumor-free, whereas groups vaccinated with single Nefmut-fused antigens were only partly protected, with stronger antitumor effects in Her2/neu-immunized mice. Double-vaccinated mice also controlled tumor growth upon a later tumor cell re-challenge. Importantly, co-vaccination also contained tumors in a therapeutic immunization setting. These results showed the efficacy of EV-based vaccination against two TAAs, and represent the first demonstration that HOXB7 may be targeted in multi-antigen immunotherapy strategies.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 11","pages":"1688-1695"},"PeriodicalIF":4.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00831-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0