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The therapeutic efficacy of fusion cell (FC)-based cancer vaccine generated with whole tumor cells and dendritic cells (DCs) requires the improved immunogenicity of both cells. Treatment of whole tumor cells with ethanol resulted in blockade of immune-suppressive soluble factors such as transforming growth factor (TGF)-β1, vascular endothelial growth factor, and IL-10 without decreased expression of major histocompatibility complex (MHC) class I and the MUC1 tumor-associated antigen. Moreover, the ethanol-treated tumor cells expressed “eat-me” signals such as calreticulin (CRT) on the cell surface and released immunostimulatory factors such as heat shock protein (HSP)90α and high-mobility group box 1 (HMGB1). A dual stimulation of protein-bound polysaccharides isolated from Coriolus versicolor (TLR2 agonist) and penicillin-inactivated Streptococcus pyogenes (TLR4 agonist) led human monocyte-derived DCs to produce HSP90α and multiple cytokines such as IL-12p70 and IL-10. Interestingly, incorporating ethanol-treated tumor cells and TLRs-stimulated DCs during the fusion process promoted fusion efficiency and up-regulated MHC class II molecules on a per fusion basis. Moreover, fusions of ethanol-treated tumor cells and dual TLRs-stimulated DCs (E-tumor/FCs) inhibited the production of multiple immune-suppressive soluble factors including TGF-β1 and up-regulated the production of IL-12p70 and HSP90α. Most importantly, E-tumor/FCs activated T cells capable of producing high levels of IFN-γ, resulting in augmented MUC1-specific CTL induction. Collectively, our results illustrate the synergy between ethanol-treated whole tumor cells and dual TLRs-stimulated DCs in inducing augmented CTL responses in vitro by FC preparations. The alternative system is simple and may provide a platform for adoptive immunotherapy. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a highly aggressive and notoriously difficult to treat. As the vastmajority of patients are diagnosed at advanced stage of the disease, only a small population is curative by surgical resection. Although gemcitabine-based chemotherapy is typically offered as standard of care, most patients do not survive longer than 6 months. Thus, new therapeutic approaches are needed. Pancreatic cancer cells that develop gemcitabine resistance would still be suitable targets for immunotherapy. Therefore, one promising treatment approach may be immunotherapy that is designed to target pancreatic-cancer-associated antigens. In this paper, we detail recent work in immunotherapy and the advances in concept of combination therapy of immunotherapy and chemotherapy. We offer our perspective on how to increase the clinical efficacy of immunotherapies for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Lipophilic photosensitizers hold potential for cancer photodynamic therapy. We sought to develop a novel photosensitive stealth liposome (PSSL) which incorporating a lipophilic photosensitizer into its lipid bilayer and to examine its photoactivity.We prepared PSSL composed of lipophilic chlorin e6 (Ce6) ester, dilauroylphosphatidylcholine, dioleoylphosphatidylethanolamine and distearoyl-phosphoethanolamine-N-[poly (ethylene glycol) 2000] and evaluated its photodynamic effect against gastric cancer cell lines and tumor-bearing nude mice models.In gastric cancer cell lines, LC80 of PSSL was a maximum of 53 times as low as that of Ce6 sodium salt (Ce6-Na). PSSL completely destroyed all tumors in animal models and tumor recurrence levels were minimal (1.5±0.9%).PSSL achieved greater photodynamic effects in gastric cancer cell lines and in murine models than Ce6-Na. PSSL holds promise for photodynamic therapy for gastric cancer. [Copyright &y& Elsevier]

Date M, Fukuchi K, Namiki Y, Okumura A, Morita S, Takahashi H, Ohura K. Therapeutic effect of photodynamic therapy using PAD-S31 and diode laser on human liver cancer cells. Liver International 2004: DOI: 10.1111/j.1478-3231.2004.0902.x. © Blackwell Munksgaard 2004 Photodynamic therapy (PDT) is an effective local cancer treatment which a photosensitizer is administered and the tumor is irradiated with light. We examined the effect of PDT using PAD-S31 as the photosensitizer, and the 670 nm diode laser on human hepatocellular carcinomas (HCCs). Huh-7, HepG2 and Hep3B cell lines were used in the all experiments. Cell viability was determined by a modified MTT assay. Two methods were used for the determination of apoptosis: terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling assay and detection of fragmented mono- and oligo-nucleosomes by enzyme-linked immunosorbent assay. The caspase activity was measured by fluorometric assay. Cytochrome c in cytosolic fraction was determined using a human cytochrome c immunoassay. Xenografts of human oral HCC cells were generated in KSN S1c nude mice. In vitro PDT showed excellent cytotoxicity that was a function of laser energy, drug concentration and time to the hepatoma cell lines. The combined use of PAD-S31 and laser irradiation showed excellent anti-tumor activity without severe side-effect against human hepatoma xenografts in nude mice. PDT-mediated cell death occurred predominantly by apoptosis in vitro and in vivo. Furthermore, this treatment initiates early cytochrome c release, followed by late caspase-3 and -9 activation. Our study demonstrates that PDT using PAD-S31 and the diode laser induces apoptosis that is mediated by cytochrome c release and caspase activation in human liver cancer cell lines. It is expected that this therapy will be clinically useful for the treatment of patients with HCC. [ABSTRACT FROM AUTHOR]

Abstract: Magnetic carriers with efficient loading, delivery, and release of drugs are required for magnetically guided drug delivery system (DDS) as the potential cancer therapy. The present article describes the fabrication of porous FePt capsules approximately 340 nm in diameter with large pores of 20 nm in an ultrathin shell of 10 nm and demonstrates their application to a magnetically guided DDS in vitro. An aqueous anti-cancer drug is easily introduced in the hollow space of the capsules without external stimuli and released to cancer cells on cue through the magnetic shell composed of an ordered-alloy FePt network structure, which exhibits superparamagnetic features at approximately body temperature. The drug-loaded magnetic capsules coated with a lipid membrane are efficiently guided to the cancer cells within 15 min using a NdFeB magnet (0.2 T), and more than 70% of the cancer cells are destroyed. [Copyright &y& Elsevier]