Dendritic cell tumors

Kao JY, Gong Y, Chen CM, Zheng QD, Chen JJ Tumor-derived TGF-(5 reduces the efficacy of dendritic cell/tumor fusion vaccine. J Immunol 2003 170 3806-3811. 

Yu H, Gibson JA, Pinkus GS, et al. Podoplanin (D2-40) is a novel marker for follicular dendritic cell tumors. Am J Clin Pathol. 2007 128 776-782. 

Smooth muscle tumors Peripheral nerve sheath tumors Paraganglioma Solitary fibrous tumor Follicular dendritic cell tumor Langerhans cell histiocytosis Secondary tumors... 

Histiocytic tumors, dendritic cell tumors, AML (M4/M5), giant cell tumors... 

Reed-Sternberg cells in classic Fiodgkin s lymphoma, follicular and interdigitating dendritic cell tumors... 

Zhang M, Berndt BE, Chen JJ, Kao JY. Expression of a soluble TGE-beta receptor by tumor cells enhances dendritic cell/tumor fusion vaccine efficacy. J Immunol 2008 181 3690-3697. 

Other proliferative diseases, for example, gastric carcinoma, breast cancer, T cell lymphoma, follicular dendritic cell tumors Immunosuppressed graft recipients post-transplant lymphoproliferative disease AIDS patients Burkitt s and Hodgkin s lymphomas, CNS lymphomas, leiosarcomas, oral hairy leukoplakia Kaposi s sarcoma, primary effusion lymphoma, multicentric Castleman s disease... 

Heckelsmiller, K. et al., Combined dendritic cell- and CpG oligonucleotide-based immune therapy cures large murine tumors that resist chemotherapy, Eur. J Immunol, 32, 3235, 2002. 

Ruby, C., Leid, M., and Kerkvliet, N.I., 2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses tumor necrosis factor-a and anti-CD40-induced activation of NF-KB/Rel in dendritic cells p50 homodimer activation is not affected, Molec. Pharmacol., 62, 722, 2002. 

Provenge is a cancer vaccine using cell therapy technique. Dendritic cells are removed from patients. These cells are treated with the prostate-specific antigen prostatic acid phosphatase (PAP), which is present in 95% of prostate cancer cases. The activated dendritic cells are returned to the patients and they stimulate the T cells to destroy cancer cells expressing the PAP, thus treating the tumor. 

While the FDA is adopting a cautious approach to cancer vaccine, such as DCVax-Brain, the Swiss Institute of Public Health has conditionally allowed the use of this vaccine by patients. DCVax consists of a patient s dendritic cells that have been pulsed with antigens derived from a tumor cell lysate prepared from surgically resected glioblastoma (brain cancer) tissue. It was developed by a company in the United States but has not yet been approved by the FDA. 

One of the important relay stations in the immune system activation is the dendritic cell. Activation of these cells causes the most efficient stimulation of T-cells, which in turn attack tumor cells (9). This turned the dendritic cells (DCs) into the focus of modern immune research and therapy. However, another difficulty appeared that became a problem recently. In order to activate the dendritic cell, the antigen has to be present in the cytosol and has to be processed there further this is not an easy task to perform. 

Figure 6 Immunopotentiating reconstituted influenza virosomes (IRIV) adjuvant effects in the induction of tumor associated antigen-specific cytotoxic T cell. CD14-negative cells from a healthy donor peripheral blood mononuclear cells were cocultured with autologous immature dendritic cells (iDC) in the presence of Melan-A/Mart-l27-35, alone (A) or supplemented with either control liposomes (B) or IRIV (1 50, C). On day 7, culture cells were restimulated with Melan-A/MART-127-35 pulsed iDC and cultured for six further days [see Materials and Methods ]. On day 7 after restimulation cells were stained with fluorescein isothiocyanate-conjugated anti-CD8 and phosphatidylethanolamine-conjugated HL A-A0201 /Melan-A/MART -127-3 5 tetramers. Source From Ref. 6.

To review, in an experimental mouse model, LPDI/E7 vaccination both prevents the establishment of metastatic E7-expressing tumors in naive mice through an induced E7-specific T-cell immune response and, in mice with previously established E7-expressing tumors, causes tumor regression with one subcutaneous injection of LPDI/E7 [Han SJ, et al. Subcutaneous antigen loading of dendritic cells by liposome-protamine-DNA (LPD) nanoparticles results in their activation and induction of specific antitumor immune response (impublished)]. A robust immune response follows administration of LPDI/ peptide particles, which can be used as either a preventative or therapeutic cancer vaccination strategy due to the ability of the particles to prevent and eliminate tumors, respectively, in mouse models. 

Nestle, F.O., S. Alijagic, M. Gilliet, Y. Sun, S. Grabbe, R. Dummer, G. Burg, and D. Schadendorf, Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med, 1998. 4(3) 328-32. 

Cytokines have been under clinical investigation as adjuvants to vaccines, and IFNs and IL-2 have shown some positive effects in the response of human subjects to hepatitis vaccine. IL-12 and GM-CSF have also shown adjuvant effects with vaccines. GM-CSF is of particular interest because it promotes recruitment of professional antigen-presenting cells such as the dendritic cells required for priming naive antigen-specific T-lymphocyte responses. There are some claims that GM-CSF can itself stimulate an antitumor immune response, resulting in tumor regression in melanoma and prostate cancer. 

Van Tendeloo, V.F., Ponsaerts, P, Lardon, F., et al. (2001). Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells. Blood, 98, 49-56. 

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