» Articles » PMID: 18565854

In Vivo Trafficking and Survival of Cytokine-induced Killer Cells Resulting in Minimal GVHD with Retention of Antitumor Activity

Overview
Journal Blood
Publisher Elsevier
Specialty Hematology
Date 2008 Jun 21
PMID 18565854
Citations 91
Authors
Affiliations
Soon will be listed here.
Abstract

Cytokine-induced killer (CIK) cells are ex vivo-expanded T lymphocytes expressing both natural killer (NK)- and T-cell markers. CIK cells are cytotoxic against autologous and allogeneic tumors. We previously showed that adoptive transfer of allogeneic CIK cells in a murine model caused minimal graft-versus-host disease (GVHD). However, the precise mechanism of reduced GVHD is not fully understood. Therefore, we evaluated the trafficking and survival of luciferase-expressing CIK cells in an allogeneic bone marrow transplant model. The initial trafficking patterns of CIK cells were similar to conventional T cells that induced GVHD; however, CIK cells infiltrated GVHD target tissues much less and transiently. CIK cells accumulated and persisted in tumor sites, resulting in tumor eradication. We evaluated different properties of CIK cells compared with conventional T cells, demonstrating a slower division rate of CIK cells, higher susceptibility to apoptosis, persistent increased expression of interferon gamma (IFN-gamma), and reduced acquisition of homing molecules required for entry of cells into inflamed GVHD target organs that lack expression of NKG2D ligands recognized by CIK cells. Due to these properties, allogeneic CIK cells had reduced expansion and caused less tissue damage. We conclude that CIK cells have the potential to separate graft-versus-tumor effects from GVHD.

Citing Articles

Cytokine-Induced Killer Cell Immunotherapy Reduces Recurrence in Patients with Early-Stage Hepatocellular Carcinoma.

Kim D, Kim E, Lee J, Kim M, Kim B, Kim S Cancers (Basel). 2025; 17(4).

PMID: 40002160 PMC: 11853259. DOI: 10.3390/cancers17040566.


CAR-CIK vs. CAR-T: benchmarking novel cytokine-induced killer cells as solid tumor immunotherapy in ErbB2+ rhabdomyosarcoma.

Moser L, Heim C, Koschade S, Wendel P, Bozkurt S, Harenkamp S Front Immunol. 2025; 16:1485817.

PMID: 39963129 PMC: 11831232. DOI: 10.3389/fimmu.2025.1485817.


Chimeric antigen receptor-natural killer (CAR-NK) cell immunotherapy: A bibliometric analysis from 2004 to 2023.

Li W, Feng J, Peng J, Zhang X, Aziz A, Wang D Hum Vaccin Immunother. 2024; 20(1):2415187.

PMID: 39414236 PMC: 11486046. DOI: 10.1080/21645515.2024.2415187.


Generation of dual-attribute iTNK cells from hPSCs for cancer immunotherapy.

Zhang Y, He Y, Dai C, Zhou Z, Miao Y, Zhao Z Cell Rep Methods. 2024; 4(9):100843.

PMID: 39216483 PMC: 11440056. DOI: 10.1016/j.crmeth.2024.100843.


CAR-NK Cell Therapy: A Transformative Approach to Overcoming Oncological Challenges.

Li W, Wang X, Zhang X, Aziz A, Wang D Biomolecules. 2024; 14(8).

PMID: 39199421 PMC: 11352442. DOI: 10.3390/biom14081035.


References
1.
Beilhack A, Schulz S, Baker J, Beilhack G, Wieland C, Herman E . In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets. Blood. 2005; 106(3):1113-22. PMC: 1895168. DOI: 10.1182/blood-2005-02-0509. View

2.
Edinger M, Cao Y, Verneris M, Bachmann M, Contag C, Negrin R . Revealing lymphoma growth and the efficacy of immune cell therapies using in vivo bioluminescence imaging. Blood. 2002; 101(2):640-8. DOI: 10.1182/blood-2002-06-1751. View

3.
Introna M, Borleri G, Conti E, Franceschetti M, Barbui A, Broady R . Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study. Haematologica. 2007; 92(7):952-9. DOI: 10.3324/haematol.11132. View

4.
Edinger M, Hoffmann P, Ermann J, Drago K, Fathman C, Strober S . CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003; 9(9):1144-50. DOI: 10.1038/nm915. View

5.
Chan J, Hamilton C, Cheung M, Karimi M, Baker J, Gall J . Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: a preclinical study. Clin Cancer Res. 2006; 12(6):1859-67. DOI: 10.1158/1078-0432.CCR-05-2019. View