Transfer of in vitro expanded T lymphocytes after activation with dendritomas prolonged survival of mice challenged with EL4 tumor cells.
Adoptive T cell transfer after in vitro expansion represents an attractive cancer immunotherapy. The majority of studies so far have been focusing on the expansion of tumor infiltrated lymphocytes (TIL) and some have shown very encouraging results. Recently, we have developed a unique tumor immune response activator, dendritomas, by fusion of dendritic cells and tumor cells. Animal studies and early clinical trials have shown that dendritomas are able to activate tumor specific immune responses. In this study, we hypothesized that naïve T cells can be primed with dendritomas and expanded in vitro to develop an adoptive transfer therapy for patients who do not have solid tumors, such as leukemia. T cells were isolated and purified from lymph nodes of mice. The cells were then incubated with dendritomas made from syngeneic DCs and tumor cells and expanded in vitro using Dynabeads mouse CD3/CD28 T cell expander for approximately three weeks. The in vitro primed and expanded T cells showed tumor cell specific CTL activity and increased secretion of IFN-gamma. Tumor bearing mice receiving the in vitro expanded T cells survived significantly longer than control mice. Furthermore, the depletion of regulator T cells enhanced the survival of the mice that received the adoptive transfer therapy.
Li
Jinhua
J
Oncology Research Institute, Greenville Hospital System University Medical Center, Greenville, SC, USA.
Theofanous
Leigh
L
Stickel
Sara
S
Bouton-Verville
Hilary
H
Burgin
Kelly E
KE
Jakubchak
Susan
S
Wagner
Thomas E
TE
Wei
Yanzhang
Y
D000818:Animals; D018106:CD28 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000628:therapy*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*; D023041:Xenograft Model Antitumor Assays
D018106:CD28 Antigens; D017252:CD3 Complex