Background: Cancer immunotherapy directs the immune system to attack tumor cells by targeting tumor-associated antigens. We manufacture fully personalized monocytederived dendritic cell-based vaccines (DC-based vaccines) that are evaluated in investigator-initiated clinical trial "Combined antitumor therapy with ex vivo manipulated dendritic cells producing interleukin-12 in children, adolescents and young adults with progressive, recurrent or primarily metastatic high-risk tumors". Methods: DC-based vaccine, called MyDendrix, is manufactured under GMP in Clean rooms of the Department of Pharmacology Masaryk University Brno. Mononuclear cells are collected by apheresis. Monocytes cultivated with IL-4 and GM-CSF differentiate into DC and are exposed to autologous tumor lysate antigens. Semi-maturated DC are aliquoted and cryopreserved. Quality control includes viability, IL-12, IL-10 production, surface markers expression, stimulation of allogenic and autologous T-cells. Vaccines are administered intradermally every 2-4 weeks, up to 35 doses. Detailed immunomonitoring of peripheral blood leucocytes subsets at the baseline and during vaccination is performed. That includes routine examined peripheral blood parameters, monocyte subsets, MDSC, specific lymphocyte subsets including Tregs, effector Tcells, NKT-like cells. Moreover, ex vivo functional immunomonitoring based on autologous T-cell stimulation by DC vaccine is performed. Results: The primary endpoint of the clinical trial is the assessment of safety by the analysis of occurrence of AESI (adverse events of special interest) in adaptive 5 þ 5þ5 þ 5 design. As of to date, 11 patients have been treated. No AESI was detected. Local skin reaction is usually mild and self-limiting. De facto size and redness of induration at vaccination sites can be reflected by T-cells stimulation after vaccination. Ex vivo T-cell reactivity was enhanced upon vaccination. Conclusions: Intradermal treatment with the DC-based anti-cancer vaccine is, according to interim analysis, safe and well-tolerated. Ex vivo assessment of pre-and post-vaccination DC-stimulated autologous T-cell activation has shown that anti-cancer vaccine-enhanced pre-existing T-cell response to tumor antigens.
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