Anti-leukemia activity of in vitro-expanded human gamma delta T cells in a xenogeneic Ph+ leukemia model. PLoS One 2011 Feb 03;6(2):e16700
Date
02/10/2011Pubmed ID
21304898Pubmed Central ID
PMC3033392DOI
10.1371/journal.pone.0016700Scopus ID
2-s2.0-79751483980 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
Gamma delta T cells (GDTc) lyse a variety of hematological and solid tumour cells in vitro and in vivo, and are thus promising candidates for cellular immunotherapy. We have developed a protocol to expand human GDTc in vitro, yielding highly cytotoxic Vgamma9/Vdelta2 CD27/CD45RA double negative effector memory cells. These cells express CD16, CD45RO, CD56, CD95 and NKG2D. Flow cytometric, clonogenic, and chromium release assays confirmed their specific cytotoxicity against Ph(+) cell lines in vitro. We have generated a fluorescent and bioluminescent Ph(+) cell line, EM-2eGFPluc, and established a novel xenogeneic leukemia model. Intravenous injection of EM-2eGFPluc into NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice resulted in significant dose-dependent bone marrow engraftment; lower levels engrafted in blood, lung, liver and spleen. In vitro-expanded human GDTc injected intraperitoneally were found at higher levels in blood and organs compared to those injected intravenously; GDTc survived at least 33 days post-injection. In therapy experiments, we documented decreased bone marrow leukemia burden in mice treated with GDTc. Live GDTc were found in spleen and bone marrow at endpoint, suggesting the potential usefulness of this therapy.
Author List
Siegers GM, Felizardo TC, Mathieson AM, Kosaka Y, Wang XH, Medin JA, Keating AAuthor
Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Proliferation
Cells, Cultured
Cytotoxicity, Immunologic
Disease Models, Animal
Humans
Immunotherapy, Adoptive
K562 Cells
Leukemia
Male
Mice
Mice, Inbred NOD
Mice, Transgenic
Philadelphia Chromosome
Receptors, Antigen, T-Cell, gamma-delta
T-Lymphocytes, Cytotoxic
Transplantation, Heterologous