Increasing the Potency of CD-34-DC Vaccines

Baylor Research Institute, Dallas TX

Investigators

Linked publications & trials

Abstract

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