| Author | Zhang, Ying | |
| Author | Xie, Xuemei | |
| Author | Yeganeh, Pourya Naderi | |
| Author | Lee, Dian-Jang | |
| Author | Valle-Garcia, David | |
| Author | Meza-Sosa, Karla F | |
| Author | Junqueira, Caroline | |
| Author | Su, Jiayu | |
| Author | Luo, Hongbo R | |
| Author | Hide, Winston | |
| Author | Lieberman, Judy | |
| Access date | 2022-02-11T17:41:54Z | |
| Available date | 2022-02-11T17:41:54Z | |
| Document date | 2021 | |
| Citation | ZHANG, Ying et al. Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown. Proc Natl Acad Sci USA, v. 118n. 9, e2022830118, 2021. doi: 10.1073/pnas.2022830118. | pt_BR |
| ISSN | 0027-8424 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/51160 | |
| Language | por | pt_BR |
| Publisher | National Academy of Sciences | pt_BR |
| Rights | restricted access | pt_BR |
| Title | Immunotherapy for breast cancer using EpCAM aptamer tumor-targeted gene knockdown | pt_BR |
| Type | Article | |
| Abstract | New strategies for cancer immunotherapy are needed since most solid tumors do not respond to current approaches. Here we used epithelial cell adhesion molecule EpCAM (a tumor-associated antigen highly expressed on common epithelial cancers and their tumor-initiating cells) aptamer-linked small-interfering RNA chimeras (AsiCs) to knock down genes selectively in EpCAM+ tumors with the goal of making cancers more visible to the immune system. Knockdown of genes that function in multiple steps of cancer immunity was evaluated in aggressive triple-negative and HER2+ orthotopic, metastatic, and genetically engineered mouse breast cancer models. Gene targets were chosen whose knockdown was predicted to promote tumor neoantigen expression (Upf2, Parp1, Apex1), phagocytosis, and antigen presentation (Cd47), reduce checkpoint inhibition (Cd274), or cause tumor cell death (Mcl1). Four of the six AsiC (Upf2, Parp1, Cd47, and Mcl1) potently inhibited tumor growth and boosted tumor-infiltrating immune cell functions. AsiC mixtures were more effective than individual AsiC and could synergize with anti–PD-1 checkpoint inhibition. | pt_BR |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children's Hospital. Boston, MA, USA/Department of Pediatrics., Harvard Medical School. Boston, MA, USA. | pt_BR |
| Affilliation | Department of Pathology. Harvard Medical School. . Boston, MA, USA./ Department of Lab Medicine and The Stem Cell Program. Boston Children's Hospital. Boston, MA, USA/The State Key Laboratory of Experimental Hematology. Institute of Hematology and Blood Diseases Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College. Tianjin, China. | pt_BR |
| Affilliation | Beth Israel Deaconess Medical Center. Harvard Medical School. Boston, MA, USA. | pt_BR |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children's Hospital. Boston, MA, USA/Department of Pediatrics., Harvard Medical School. Boston, MA, USA. | pt_BR |
| Affilliation | Divison of Newborn Medicine and Epigenetics Program. Department of Medicine. Boston Children's Hospital. Boston, MA, USA./ Department of Cell Biology. Harvard Medical School. Boston, MA, USA/Laboratorio de Neuroinmunobiología. Departamento de Medicina Molecular y Bioprocesos. Instituto de Biotecnología, Universidad Nacional Autónoma de México. Cuernavaca, México. | pt_BR |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children's Hospital. Boston, MA, USA/Department of Pediatrics., Harvard Medical School. Boston, MA, USA/Laboratorio de Neuroinmunobiología. Departamento de Medicina Molecular y Bioprocesos. Instituto de Biotecnología, Universidad Nacional Autónoma de México. Cuernavaca, México. | pt_BR |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children's Hospital. Boston, MA, USA/Department of Pediatrics., Harvard Medical School. Boston, MA, USA/ René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte,MG, Brazil. | pt_BR |
| Affilliation | Department of Pathology. Harvard Medical School. . Boston, MA, USA/ Department of Lab Medicine and The Stem Cell Program. Boston Children's Hospital. Boston, MA, USA/School of Life Sciences. Center for Bioinformatics, Peking University. Beijing, China/Center for Statistical Science. Peking University. Beijing, China. | pt_BR |
| Affilliation | Department of Pathology. Harvard Medical School. . Boston, MA, USA/Department of Lab Medicine and The Stem Cell Program. Boston Children's Hospital. Boston, MA, USA. | pt_BR |
| Affilliation | Beth Israel Deaconess Medical Center. Harvard Medical School. Boston, MA, USA. | pt_BR |
| Affilliation | Program in Cellular and Molecular Medicine. Boston Children's Hospital. Boston, MA, USA/Department of Pediatrics., Harvard Medical School. Boston, MA, USA. | pt_BR |
| Subject | EpCAM aptamer | pt_BR |
| Subject | gene knockdown | pt_BR |
| Subject | immunotherapy | pt_BR |
| Subject | checkpoint blockade | pt_BR |
| Subject | CD47 | pt_BR |
