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Laboratory for Molecular and Cellular Therapy (LMCT) of the Department of Immunology-Physiology

In 2004 a special type of government funding gave birth to the Industrial Research Fund (IOF – Industrieel Onderzoeksfonds).

This funding supports the IOF knowledge centers at the Vrije Universiteit Brussel in carrying out outstanding strategic research and further developing new application-oriented inventions with economic potential. The first priority of the IOF funds is the further establishment of a portfolio of potentially applicable and transferable know-how with economic and societal value.

Keywords

  • immunotherapy
  • translational research
  • malignant melanoma
  • denditric cells
  • cancer
  • HIV treatment

Main objectives

The LMCT has a long-term interest in the immunobiology of antigen presenting cells (dendritic cells) and experience in immunotherapy (going back to a fruitful collaboration and link with the Stanford University). The group has developed in vitro systems for the large scale production of clinical grade dendritic cells (DC).

In order to produce optimal DC-based therapeutic vaccines, the group has optimized the genetic modification of DC by electroporation with in vitro synthesized mRNA and lentiviral vectors. Manipulation of the mRNA or cDNA encoding the antigens of interest ensures an optimal presentation of antigenic epitopes by both HLA class I and class II molecular complexes.

Strategic and applied research

Objectives of our research activities and ongoing projects are:

  • Understanding the immunobiology of murine and human dendritic cells using a wide variety of up-to-date technologies  :
  • si-RNAs
  • sh-RNAs
  • micro-RNAs
  • messenger RNA
  • lentiviral and retroviral transduction of dendritic cells
  • in vivo real time imaging studies, …
  • Optimization of immunization protocols with  selected effectordendritic cell; in vitro and in preclinical murine tumor models and in SCID/NOD mice reconstituted with peripheral blood mononuclear cells from cancer patients and autologous monocyte-derived DC. These data provide the scientific base to optimize the strategies used for clinical pilot studies.
  • GMP production of clinical grade and GMP mRNA to be used for the electroporation of DC and novel immunization strategies.
  • Preparation of clinical study protocols for clinical pilot studies using DC either loaded with peptide epitopes or electroporated with defined tumor antigen encoding mRNA or HIV antigens.
  • Clinical pilot-trials using multiple peptides or mRNA and addressing critical parameters such as:
  • effector-type of DCs
  • frequency of immunization
  • dose of DCs
  • combination with modalities targeting suppressive regulatory T cells (e.g. passive therapy with anti-IL-2 receptor antibodies, with IL-2-toxine) therapy, with neutralizing anti-TGF antibodies) in cancer and HIV.

Potentially applicable and transferable knowhow with economic value

The main focus and interest of the LMCT are the development of innovative strategies for the treatment of cancer and HIV.

Technology Offer(s)

Enhancing the T-cell stimulatory capacity of human dendritic cells and their use in cancer vaccination (patent pending) – inventors: Kris Thielemans, Aude Bonehill

Equipment & Infrastructure

The total surface area of the LMCT is +/- 720m2. The LMCT has a fully equipped clean room facility for the production of clinical grade cellular vaccines according to the current criteria of GLP/GMP. A GMP-mRNA production facility is under construction. The group is the coordinating laboratory and the principal investigator of several phase I/II clinical pilot studies of DC-based vaccines for the treatment of cancer patients and HIV infected individuals. Two BL-2 and a BL-3 laboratory have been incorporated in the LMCT infrastructure in 2000. These BL-2/3 laboratories are also fully equipped with biosafety cabinets, CO2incubators, table-top centrifuges, an ultracentrifuge, etc.

Research collaboration

  • Intra-university

    The LMCT is located on the Life Science Campus of the VUB and is associated with the Medical School and the University Hospital UZ Brussel. Kris Thielemans has a dual appointment in both Medical School and in the University Hospital. To optimize the transfer of the translational research activities a “HIV-Cell therapy unit” and a “Cancer-Cell Therapy Unit” have been established with the clinical scientists of the Department of Infectious Diseases and the Department of Medical Oncology & Hematology.
  • Inter-university & research centers
     
  • Stanford University Medical School
  • The group has a long-lasting collaboration with experts in the field of DC biology in EU and the US and participates in several international programs funded by the EU.

Networks

The LMCT is the coordinator of a FWO-V funded Belgian Scientific Network on Dendritic Cell Biology.

Spin-off’s

The research group was co-founder of the spin-off BruCells NV/SA.

Vrije Universiteit Brussel - Faculty of Medicine and Pharmacy
Laarbeeklaan 103 – B-1090 Brussels – Belgium
[T] +32 (0)2 477 45 69
[F] +32 (0)2 477 45 68
Head: Kris THIELEMANS
[E] kris.thielemans@vub.ac.be
Scientific contact: Aude Bonehill
[E] aude.bonehill@vub.ac.be
GROUP LMCT: 15 researchers