Current status of ex vivo gene therapy for hematological disorders: a review of clinical trials in Japan around the world

Tani, Kenzaburo

doi:10.1007/s12185-016-2030-2

Cited by 9 publications

(2 citation statements)

References 85 publications

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“…Ex vivo gene therapy was originally initiated with hematopoietic stem cells (HSCs) to cure monogenic genetic diseases, including adenosine deaminase severe combined immunodeficiency (ADA-SCID), X-linked-SCID, and X-linked adrenoleukodystrophy (ALD) ( Cartier et al, 2009 ; Cicalese et al, 2018 ; Hacein-Bey-Abina et al, 2002 ; Naldini, 2011 ; Tani, 2016 ). Recently, chimeric antigen receptor (CAR)-T cells have emerged as a powerful treatment for acute lymphocytic leukemia ( Kalos et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Improving the Safety of Mesenchymal Stem Cell-Based Ex Vivo Therapy Using Herpes Simplex Virus Thymidine Kinase

Bashyal

Lee²,

Chang³

et al. 2022

Molecules and Cells

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Human mesenchymal stem cells (MSCs) are multipotent stem cells that have been intensively studied as therapeutic tools for a variety of disorders. To enhance the efficacy of MSCs, therapeutic genes are introduced using retroviral and lentiviral vectors. However, serious adverse events (SAEs) such as tumorigenesis can be induced by insertional mutagenesis. We generated lentiviral vectors encoding the wild-type herpes simplex virus thymidine kinase (HSV-TK) gene and a gene containing a point mutation that results in an alanine to histidine substitution at residue 168 (TK(A168H)) and transduced expression in MSCs (MSC-TK and MSC-TK(A168H)). Transduction of lentiviral vectors encoding the TK(A168H) mutant did not alter the proliferation capacity, mesodermal differentiation potential, or surface antigenicity of MSCs. The MSC-TK(A168H) cells were genetically stable, as shown by karyotyping. MSC-TK(A168H) responded to ganciclovir (GCV) with an half maximal inhibitory concentration (IC 50 ) value 10-fold less than that of MSC-TK. Because MSC-TK(A168H) cells were found to be non-tumorigenic, a U87-TK(A168H) subcutaneous tumor was used as a SAE-like condition and we evaluated the effect of valganciclovir (vGCV), an oral prodrug for GCV. U87-TK(A168H) tumors were more efficiently ablated by 200 mg/kg vGCV than U87-TK tumors. These results indicate that MSC-TK(A168H) cells appear to be pre-clinically safe for therapeutic use. We propose that genetic modification with HSV-TK(A168H) makes allogeneic MSC-based ex vivo therapy safer by eliminating transplanted cells during SAEs such as uncontrolled cell proliferation.

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Section: Discussionmentioning

confidence: 99%

Improving the Safety of Mesenchymal Stem Cell-Based Ex Vivo Therapy Using Herpes Simplex Virus Thymidine Kinase

Bashyal

Lee²,

Chang³

et al. 2022

Molecules and Cells

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“…Các nhà nghiên cứu tại Đại học Hokkaido điều trị cho bệnh nhân bằng vector retrovirus nhập khẩu từ Genetic Therapy (Gaithersburg, MD), sử dụng cùng quy trình của nhóm Anderson áp dụng. Kể từ lần thử nghiệm đầu tiên này, đến nay có 58 thử nghiệm lâm sàng đã được chấp thuận; trong đó có 37 trường hợp áp dụng cho bệnh ác tính và 21 trường hợp cho bệnh bẩm sinh hoặc bệnh không ác tính (Tani, 2016). Nghiên cứu hệ gen dược học đóng vai trò quan trọng trong đáp ứng thuốc.…”

Section: Nghiên Cứu Phát Triển Và ứNg Dụng Công Nghệ Gen Trong Lĩnh V...unclassified

Current status of genetic engineering in the fields of medicine, pharmacology and agriculture in China, Japan and Korea

Hang

Hà

Hiền

2018

Vietnam J. Biotechnol.

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Research and development (R&D) of genetic engineering in Asian countries, particularly in China, Japan and Korea, have been achieved great success and applied in many aspects of the social economic fields. In the area of medicine, these nations focus on studying the diagnosis of cancers, infectious, and hereditary diseases using molecular techniques based on PCR, and next generation sequencing; implementing clinical trials by gene therapy and improving prevention with innovative vaccines such as subunit or DNA vaccines. In addition, preparatory studies on human cells or embryos utilizing CRISPR/Cas9 genome editing technology have been undertaken in hopes of finding new treatments for genetic and cancer diseases. In the field of agriculture, many Asian countries have carried out R&D and approved genetically modified crops and produtcs for releasing into the environment and utilizing for food, feed and processing. The modified traits mainly are insect resistance, virus resistance, herbicide tolerance, drought tolerance, salinity tolerance, and increased nutritional value. In general, the level of development and application of genetic engineering in these nations has outstripped in Asia, but still underdevelopment state compared to the United States, Canada and several European countries. Therefore, each country should have appropriate policies and investments to promote the application of advanced biotechnologies in the world in order to improve the quality of human life.

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Gene Therapy for Neoplastic Hematology in Transplant Setting

Castro

Kipps

2018

Advances and Controversies in Hematopoietic Transplantation and Cell Therapy

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Current status of ex vivo gene therapy for hematological disorders: a review of clinical trials in Japan around the world

Cited by 9 publications

References 85 publications

Improving the Safety of Mesenchymal Stem Cell-Based Ex Vivo Therapy Using Herpes Simplex Virus Thymidine Kinase

Improving the Safety of Mesenchymal Stem Cell-Based Ex Vivo Therapy Using Herpes Simplex Virus Thymidine Kinase

Current status of genetic engineering in the fields of medicine, pharmacology and agriculture in China, Japan and Korea

Gene Therapy for Neoplastic Hematology in Transplant Setting

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