Preclinical Toxicity Studies for Regenerative Medicine in Japan.

Autor: Shigeto J; Incubation Center for Advanced Medical Science, Kyushu University, Fukuoka, Japan. Electronic address: jshigeto@med.kyushu-u.ac.jp., Ichiki T; Incubation Center for Advanced Medical Science, Kyushu University, Fukuoka, Japan., Nii T; Incubation Center for Advanced Medical Science, Kyushu University, Fukuoka, Japan., Konno K; Incubation Center for Advanced Medical Science, Kyushu University, Fukuoka, Japan., Nakanishi Y; Incubation Center for Advanced Medical Science, Kyushu University, Fukuoka, Japan; Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan., Sugiyama D; Incubation Center for Advanced Medical Science, Kyushu University, Fukuoka, Japan; Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan.
Jazyk: angličtina
Zdroj: Clinical therapeutics [Clin Ther] 2018 Nov; Vol. 40 (11), pp. 1813-1822. Date of Electronic Publication: 2018 Oct 24.
DOI: 10.1016/j.clinthera.2018.09.007
Abstrakt: Purpose: Advances in methods designed to evaluate preclinical toxicity have not kept up with progress in regenerative medicine. Preclinical toxicity studies of regenerative therapies must be designed logically and should be flexible to accurately reflect toxicity of products under development. The purpose of this review is to discuss requirements of preclinical toxicity studies of this type developed in Japan.
Methods: We conducted MEDLINE and PubMed literature searches to identify recent reports relevant to regenerative medicine. Information regarding approved drugs and public announcements, including existing guidelines and guidance in Japan, was collected from the website of Japan's Ministry of Health, Labor and Welfare (https://www.mhlw.go.jp/index.html) and the Pharmaceuticals and Medical Devices Agency (https://www.pmda.go.jp/).
Findings: Four cell therapy products have been developed and approved in Japan so far. The principal preclinical toxicity data submitted to regulatory authorities in the Pharmaceuticals and Medical Devices Agency in Japan are summarized here. The potential for tumor formation, a major concern in such clinical applications, is assessed in 3 ways: tumor-forming capacity of the original cell, quantitation of residual pluripotent stem cells in the product, and the possibility that a tumor will form at the product's engraftment site. Although gene therapy and oncolytic virus products are under development, these types of products are not yet approved in Japan. Guidelines relevant to the development of these products are now being created based on existing guidelines and considerations established by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use.
Implications: Because of cell tropism and heterologous immunity, animal species or strains useful for preclinical studies of regenerative therapies are often restricted. Nonetheless, preclinical toxicity studies must be designed to predict results relevant to humans.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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