Novel fusion cells derived from tumor cells expressing the heterologous α-galactose epitope and dendritic cells effectively target cancer.

Tumor cells/dendritic cells (DCs) fusion cells (tumor/DC) represent a promising immunotherapeutic strategy but are still under performed in clinical trials for cancer treatment. To further boost their anticancer efficacy, here we developed a novel design for fusing dendritic cells with MDA-MB-231 cells expressing the heterologous α-galactose (α-gal) epitope and assessed its anticancer activities both in vitro and in vivo. The high expression of α-gal in MDA-MB-231 (Gal+)/DC correlated with enhanced DC activation. When applied to T cells, MDA-MB-231 (Gal+)/DC significantly stimulated T-cell proliferation and activation, promoted productions of cytokines IL-2 and IFN-γ, and enhanced T-cell-mediated cytotoxicity against MDA-MB-231 cells. MDA-MB-231 (Gal+)/DC inhibited proliferation and promoted apoptosis of tumor cells in vivo, prolonged mouse survival, and significantly boosted anticancer immunity by increasing CD4+ and CD8+ T cells systemically and elevating serum levels of cytokines and IgG. These results suggested that fusing dendritic cells with tumor cells expressing the heterologous α-gal epitope provides a novel therapeutic strategy for cancer treatment.

Vincristine-Loaded and sgc8-Modified Liposome as a Potential Targeted Drug Delivery System for Treating Acute Lymphoblastic Leukemia.

Cytotoxic compounds vincristine sulphate (VCR) is widely used to against hemato-oncology, and especially the acute lymphoblastic leukemia (ALL). However, VCR's full therapeutic potential has been limited by its dose-limiting neurotoxicity, classically resulting in autonomic and peripheral sensory-motor neuropathy. Therefore, we developed a targeted liposomal drug delivery system (sgc8/VCR-Lipo) for improving the therapeutic effects of VCR against leukemia and reducing its systematic adverse effects. sgc8/VCR-Lipo could specifically bind to CCRF-CEM cells and significantly inhibit proliferation of cancer cells in vitro and tumor growth in vivo. The sgc8/VCR-Lipo nanoparticles may improve the anti-tumor efficacy of VCR and reduce side effects induced by non-specific drug release. These results suggest that our findings provide scientific evidence for developing novel aptamer-based targeted drug delivery systems for leukemia treatment.

Isolation of Fibroblast-Activation Protein-Specific Cancer-Associated Fibroblasts.

The current study is to develop a gentle and efficient method for purification of fibroblast-activation protein positive (FAP+) cancer-associated fibroblasts (CAFs) from tumor tissues. Fresh tissues were isolated from BALB/c-Nude mice bearing human liver cancer cell line (HepG2), fully minced and separated into three parts, and digested with trypsin digestion and then treated with collagenase type IV once, twice, or thrice, respectively. Finally, the cells were purified by using FAP magnetic beads. The isolated CAFs were grown in culture medium and detected for the surface expression of fibroblast-activation protein (FAP). The number of adherent cells which were obtained by digestion process with twice collagenase type IV digestion was (5.99 ± 0.18) × 104, much more than that with the only once collagenase type IV digestion (2.58 ± 0.41) × 104 (P < 0.0001) and similar to thrice collagenase type IV digestion. The percentage of FAP+ CAFs with twice collagenase type IV digestion (38.5%) was higher than that with the only once collagenase type IV digestion (20.0%) and little higher than thrice collagenase type IV digestion (37.5%). The FAP expression of CAFs was quite different from normal fibroblasts (NFs). The fibroblasts isolated by the innovation are with high purity and being in wonderful condition and display the features of CAFs.

Enhanced anti-tumor immunity against breast cancer induced by whole tumor cell vaccines genetically modified expressing α-Gal epitopes.

Whole tumor cell vaccines have shown much promise, but demonstrated poor efficiency in phase III trials. In this study, we modified MDA-MB­231 tumor cells (MDA-MB­231Gal+) to express α-1, 3-galactosyltransferase (α-1, 3-GT) protein, to potentially enhance antitumor effect of whole tumor cell vaccines. MDA-MB­231 tumor cell vaccines were transfected with a reconstructed lentiviral containing α-1, 3-GT genes. Tumor growth, tumorigenesis and survival of Hu-NOD-SCID mice were observed when tumor-bearing mice were injected with tumor cell vaccines. Proliferation and apoptosis in MDA-MB­231 tumor xenografts were observed by immunohistochemistry. The levels of cytokine secretion in the serum of mice were tested by ELISA. CD8+ T cells infiltrating tumors were assessed by flow cytometry. MDA-MB­231Gal+ cells expressed active α-1, 3-GT and produced α-Gal in vitro. MDA-MB­231Gal+ cell vaccines suppressed tumor growth and tumorigenesis in immunized Hu-NOD-SCID mice. Additionally, decrease of TGF-ß, IL-10 and increase of INF-γ, IL-12 were observed in tumor cell vaccinated mice. Furthermore, the cell vaccines enhanced infiltration of cytotoxic CD8+ T cells in the tumor microenvironment of immunized mice. The MDA-MB­231Gal+ cell vaccines modified α-1, 3-GT genes improved the antitumor effect.