A Combination Hybrid-Based Vaccination/Adoptive Cellular Therapy to Prevent Tumor Growth by Involvement of T Cells

Abstract

Cancer immunotherapy with dendritic cell-tumor cell fusion hybrids induces polyclonal stimulation against a variety of tumor antigens, including unknown antigens. Hybrid cells can prime CTLs, which subsequently develop antitumor responses. The aim of this study was to enhance the known antitumor effect of hybrid vaccination (HC-Vacc) and hybrid-primed adoptive T-cell therapy (HC-ACT) using the poorly immunogenic Lewis lung carcinoma (LLC1) model. The strategy used was a combination of a double HC-Vacc alternating with HC-ACT (HC-Vacc/ACT). Using flat-panel volumetric computer tomography and immunohistochemistry, we showed a significant retardation of tumor growth (85%). In addition, a significant delay in tumor development, a reduction in the number of pulmonary metastases, and increased survival times were observed. Furthermore, the tumors displayed significant morphologic changes and increased apoptosis, as shown by up-regulation of gene expression of the proapoptotic markers Fas, caspase-8, and caspase-3. The residual tumor masses seen in the HC-Vacc/ACT-treated mice were infiltrated with CD4 + and CD8 + lymphocytes and showed elevated IFN; expression. Moreover, splenic enlargement observed in HCVacc/ACT-treated mice reflected the increased functionality of T cells, as also indicated by increased expression of markers for CTL activation, differentiation, and proliferation (Cd28, Icosl, Tnfrsf13, and Tnfsf14). Our findings indicate that the combination therapy of dendritic cell-tumor cell HC-Vacc/ ACT is a very effective and a promising immunotherapeutic regimen against poorly immunogenic carcinomas. [Cancer Res 2007;67(11):5443-53]

Increase of In Vivo Antitumoral Activity by CD40L (CD154) Gene Transfer Into Pancreatic Tumor Cell-Dendritic Cell Hybrids

“…Dendritic cell-tumor hybrids have been reported by several groups to be successful in increasing tumor response, particularly in combination with effector cells. 15 In our experiments, we reached an increase of fusion efficiency up to 30%. These data are similar to those obtained with other tumor cells.…”

Expression and Activity of Phosphodiesterase Isoforms during Epithelial Mesenchymal Transition: The Role of Phosphodiesterase 4

“…513804) 1.45 ms with a digital camera (DC 300 FX; Leica Microsystems) attached to the microscope. Using Qwin V3 software (Leica Microsystems), FITC and DAPI images were merged and fluorescent intensity levels were quantified as described previously (Savai et al, 2005(Savai et al, , 2007.…”

mRNA-based vaccines synergize with radiation therapy to eradicate established tumors

“…This tumor model is resistant to different kinds of therapeutic regimens (Avastin, radiation, adoptive T cell transfer) [6–8]. It is characterized by nearly complete MHC class I down regulation, a lack of known tumor rejection antigens, very aggressive growth kinetics, frequent ulceration in small tumors and rapid formation of spontaneous lung metastases from the primary solid tumor.…”