title: Retroviral Vectors for Cancer Gene Therapy.
abstract: Advances in molecular technologies have led to the discovery of many disease-related genetic mutations as well as elucidation of aberrant gene and protein expression patterns in several human diseases, including cancer. This information has driven the development of novel therapeutic strategies, such as the utilization of small molecules to target specific cellular pathways and the use of retroviral vectors to retarget immune cells to recognize and eliminate tumor cells. Retroviral-mediated gene transfer has allowed efficient production of T cells engineered with chimeric antigen receptors (CARs), which have demonstrated marked success in the treatment of hematological malignancies. As a safety point, these modified cells can be outfitted with suicide genes. Customized gene editing tools, such as clustered regularly interspaced short palindromic repeats-CRISPR-associated nucleases (CRISPR-Cas9), zinc-finger nucleases (ZFNs), or TAL-effector nucleases (TALENs), may also be combined with retroviral delivery to specifically delete oncogenes, inactivate oncogenic signaling pathways, or deliver wild-type genes. Additionally, the feasibility of retroviral gene transfer strategies to protect the hematopoietic stem cells (HSC) from the dose-limiting toxic effects of chemotherapy and radiotherapy was demonstrated. While some of these approaches have yet to be translated into clinical application, the potential implications for improved cellular replacement therapies to enhance and/or support the current treatment modalities are enormous.
authors.affiliation: Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany. schambach.axel@mh-hannover.de.|REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, Germany. schambach.axel@mh-hannover.de.|Division of Hematology/Oncology, Boston Children's Hospital Harvard Medical School, Boston, MA, USA. schambach.axel@mh-hannover.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.affiliation: Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany. morgan.michael@mh-hannover.de.|REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, Germany. morgan.michael@mh-hannover.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D064130:CRISPR-Associated Proteins / Q000235:genetics / Q000378:metabolism; D064113:CRISPR-Cas Systems; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics; D000072669:Gene Editing / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012190:Retroviridae / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D014161:Transduction, Genetic
chemical_list: D014408:Biomarkers, Tumor; D064130:CRISPR-Associated Proteins; D011948:Receptors, Antigen, T-Cell
keywords: Anticancer; CAR; Cytoprotection; Gene editing; Gene transfer; Retrovirus