A safety evaluation of intravenous administration of ex vivo expanded human peripheral blood-derived NK cells: A preclinical study

Gounder, Sellamuthu Subbanna and Subramani, Baskar and Radzuan, Nur Ezzati Izyan Binti Mohd and Sait, Nurhidayah Bt Mohamad and Zain, Farah Dalila Binti Mohd and Abdullah, Basri Johan Jeet (2022) A safety evaluation of intravenous administration of ex vivo expanded human peripheral blood-derived NK cells: A preclinical study. Sains Malaysiana, 51 (1). pp. 271-284. ISSN 0126-6039, DOI https://doi.org/10.17576/jsm-2022-5101-22.

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Abstract

The use of natural killer (NK) cells in the treatment of various cancers is emerging as a promising approach in adoptive immunotherapy. However, the safety of ex vivo activated and expanded cells in in vivo conditions remain unknown. In this study, the toxicity of NK cells was evaluated at different doses, with 5 x 10(6), 20 x 10(6) and 50 x 10(6) cells injected intravenously into pre-irradiated (30Gy) immunodeficient mice twice a week for three weeks and the mice were followed-up on for 90 days. Throughout the study, no mortality, abnormal clinical signs, or behavioural changes related to the testing material were observed in either the treated or control groups of mice. There were no significant variations in food and water consumption between both genders in the NK cell treated and control groups. However, certain significant changes were observed between the groups in the clinical biochemistry and urine analysis reports. As autopsy showed no significant variations in absolute and relative organ weights between the groups, except for the livers of the treated mice. The histopathological analysis also demonstrated that there were no significant abnormalities in most of the organs of both genders, except for the liver. Some necrotic lesions were observed in the livers of both the treated and control mice, and these lesions may be due to the effects of irradiation or could be common in NOD.SCID mice. The findings of this study indicate that intravenous administration of NK cells is safe and does not cause any adverse effects up to the dose of 50 x 10(6) cells/mouse.

Item Type: Article
Funders: Nichi Asia life Science Sdn Bhd, Malaysia, Reliance life science Pvt. Ltd
Uncontrolled Keywords: Adoptive immunotherapy;Immunotherapy;Natural killer cell;NK cell toxicity;Pathology
Subjects: R Medicine
R Medicine > RB Pathology
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 04 Aug 2022 02:41
Last Modified: 04 Aug 2022 02:41
URI: http://eprints.um.edu.my/id/eprint/33545

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