57P - Immunomonitoring of patients treated with personalized dendritic cell-based vaccine (57P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Cancer Immunology and Immunotherapy
Translational Research
Presenter Lenka Fedorova
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors L. Fedorova1, L. Zdrazilova Dubska2, K. Pilatova1, P. Mudry3, P. Mazanek3, Z. Pavelka3, E. Hlavackova2, J. Sterba3, L. Flajsarova2, R. Demlova4, D. Valik1
  • 1Laboratory Medicine Department, Masaryk Memorial Cancer Institute, 65653 - Brno/CZ
  • 2Faculty Of Medicine, Masaryk University, 62500 - Brno/CZ
  • 3Department Of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno/CZ
  • 4Faculty Of Medicine, Masaryk University, Brno/CZ

Abstract

Background

Cancer immunotherapy directs the immune system to attack tumor cells by targeting tumor-associated antigens. We manufacture fully personalized monocyte-derived 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 T-cells, 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 + 5+5 + 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.

Clinical trial identification

EudraCT 2014-003388-39

Legal entity responsible for the study

Czech Ministry of Health

Funding

This work was supported by Czech Ministry of Health, projects LO1413, LM2015090, DRO (MMCI, 00209805). Academic Clinical Trial.

Disclosure

All authors have declared no conflicts of interest.