Efficacy of adoptively transferred allogeneic CIK cells on colorectal cancer: Augmentative antitumoral effects of GvHD.

Autor: Muhammadnejad S; Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Monzavi SM; Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran., Torabi-Rahvar M; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Sotoudeh M; Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Muhammadnejad A; Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran., Tavakoli-Shiraji S; Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran., Ranjbar A; Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; SABZ Biomedicals Science-Based Company, Tehran, Iran., Aghayan SS; Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; SABZ Biomedicals Science-Based Company, Tehran, Iran., Khorsand AA; Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Moradzadeh K; Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; SABZ Biomedicals Science-Based Company, Tehran, Iran., Janzamin E; Flowcyte Science-Based Company, Tehran, Iran., Ahmadbeigi N; Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; SABZ Biomedicals Science-Based Company, Tehran, Iran. Electronic address: n-ahmadbeigi@tums.ac.ir.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2023 Jan; Vol. 114, pp. 109446. Date of Electronic Publication: 2022 Dec 01.
DOI: 10.1016/j.intimp.2022.109446
Abstrakt: Objective: A preclinical study was designed to evaluate the effects of adoptively transferred cytokine-induced killer (CIK) cells on colorectal adenocarcinoma.
Methods: Forty NOG mice bearing HT-29 xenograft tumors were developed and equally divided into 2 groups of treatment and control. The mice in the treatment group received cumulatively 40-60 × 10 6 CIK cells in four divided doses.
Results: Median tumor doubling times for HT-29 xenograft tumors in the treatment and control groups were found to be 8.98 and 4.32 days; respectively. The treatment resulted in tumor growth delay (TGD) of 52.5 %. CIK cell-induced log cell kill (LCK) was found to be 0.67, which implies reduction of 78.6 % of neoplastic colorectal cells. Median length of survival in the treated mice was significantly longer than controls (57 (41-63) vs 41 (31-57) days, P < 0.001). Mice in the treatment group experienced graft-versus-host disease (GvHD) from median of day 13th after the cell therapy. LCK and TGD significantly increased after emergence of GvHD. After necropsy, tumors of the treatment group contained high levels of human-originated CD3 + , CD4 + and CD8 + cells and showed significantly lower mitotic counts (P < 0.001) and residual tumor scores (P = 0.005) than the controls (entirely negative for the mentioned CD markers). Ninety percent of the treated mice were found to be responding.
Conclusions: Adoptive transfer of allogeneic CIK cells may be an efficient antitumoral therapy for colorectal cancer. Allogeneic CIK cell-mediated GvHD may contribute to amplification of graft-versus-tumor effects of the cellular therapy.
Competing Interests: Declaration of Competing Interest N.A. has the ownership interest in SABZ Biomedicals Co., and A.R., S.A. and K.M work for SABZ Biomedicals Co. N.A. and E.J. have the ownership interest in Flowcyte Co. Both companies collaborated in this research project, though they had no influence in data collection and interpretation. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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