Using melanoma peptide loaded CD34-DCs, a composite vaccine composed of Langerhans cells and? Interstitial DCs, we have demonstrated that DC vaccines can induce tumor-specific immunity, as well as? some clinical responses. Two major questions arise: 1) Why is the composite vaccine efficient? and 2) How? can the therapeutic immunogenicity of DC vaccines be improved? With this in mind, AIM 1 will test the? hypothesis that composite DC vaccines loaded with killed allogeneic melanoma cells will have superior? therapeutic efficacy, because of i) presentation of multiple tumor antigen epitopes to both CD4 and CDS T? cells, and ii) strong allogeneic help. This will be a Phase l/ll single arm clinical trial which Primary Objective? is induction of melanoma antigen-specific CD8+T cells and Secondary Objective is induction of objective? clinical responses. The trial is powered based on the rate of induction of melanoma-specific CD8+T cell? immunity and will accrue up to 51 metastatic melanoma patients. Interim analyses will be conducted after 9? and 24 patients are enrolled to assess toxicity and immunogenicity. Immune responses will be assessed? using EPIMAX strategy. The 2 main quantitative assays involve melanoma antigen-specific IFN-gamma? release (effector memory cells) and cell proliferation (CFSE and flow cytometry; recall memory) by T cells in? short term PBMCs cultures with selected melanoma antigen-peptides.
AIM2 will assess the helper functions? of melanoma antigen-specific CD4+T cells in patients vaccinated with composite DCs loaded with killed? allogeneic melanoma cells. We want to establish an assay to measure the ability of melanoma-antigen? specific CD4+T cells to prime melanoma-antigen specific CD8+T cells.
AIM 3 will determine which DC? subset present in composite DCs vaccines primes melanoma antigen-specific CD4+T cells that help CD8+T? cells.
AIM 4 will test the hypothesis that further activation of myeloid DC vaccines, indirectly through the? activation of pDCs or exposure to IFN-a, will increase their efficacy in vitro.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA084512-05A2
Application #
7122671
Study Section
Subcommittee G - Education (NCI)
Project Start
2006-03-01
Project End
2009-05-31
Budget Start
2006-03-01
Budget End
2007-05-31
Support Year
5
Fiscal Year
2006
Total Cost
$111,981
Indirect Cost
Name
Baylor Research Institute
Department
Type
DUNS #
145745022
City
Dallas
State
TX
Country
United States
Zip Code
75204
Speake, Cate; Presnell, Scott; Domico, Kelly et al. (2015) An interactive web application for the dissemination of human systems immunology data. J Transl Med 13:196
Rongvaux, Anthony; Willinger, Tim; Martinek, Jan et al. (2014) Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol 32:364-72
Palucka, Karolina; Banchereau, Jacques (2013) Human dendritic cell subsets in vaccination. Curr Opin Immunol 25:396-402
Palucka, Karolina; Banchereau, Jacques (2013) Dendritic-cell-based therapeutic cancer vaccines. Immunity 39:38-48
Obermoser, Gerlinde; Presnell, Scott; Domico, Kelly et al. (2013) Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines. Immunity 38:831-44
Banchereau, Jacques; Thompson-Snipes, LuAnn; Zurawski, Sandra et al. (2012) The differential production of cytokines by human Langerhans cells and dermal CD14(+) DCs controls CTL priming. Blood 119:5742-9
Banchereau, Jacques; Zurawski, Sandra; Thompson-Snipes, LuAnn et al. (2012) Immunoglobulin-like transcript receptors on human dermal CD14+ dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming. Proc Natl Acad Sci U S A 109:18885-90
Palucka, Karolina; Banchereau, Jacques (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancer 12:265-77
Palucka, Karolina; Ueno, Hideki; Roberts, Lee et al. (2011) Dendritic cell subsets as vectors and targets for improved cancer therapy. Curr Top Microbiol Immunol 344:173-92
McNab, Finlay W; Berry, Matthew P R; Graham, Christine M et al. (2011) Programmed death ligand 1 is over-expressed by neutrophils in the blood of patients with active tuberculosis. Eur J Immunol 41:1941-7

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