BITCAT · Blocking Inhibition of T-cell Co-stimulation for Anti-tumour Therapy
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-05-08 → 2020-05-07
- EU contribution
- €243,353
- Participants
- 2
- Scheme
- MSCA-IF-GF
Lines connect the coordinator with its partners.
Results in brief
Blocking Inhibition of T-cell Co-stimulation for Anti-tumour Therapy
Tumors escape proper immune response by propagating immune suppression. Immunotherapy aims to enhance anti-tumor immunity. This highly relevant research area arose from advantages in immunology, genetics and oncology. Currently, immunotherapeutics are either protein or cell-based and promising approaches target immune checkpoint control, a mechanism crucial to anti-tumor T cell activity. Here, development of a new class of immunotherapeutics is proposed. To this aim, gene therapeutics will be designed to modulate expression of receptor genes involved in immune control and thus block tumor-mediated T cell inhibition. Of special interest will be the exploration of combinations of immune-oncological gene therapeutic techniques such as the CAR technique with short oligonucleotide-based approaches. During the course of the project a special focus could be established on glioblastoma (GBM), a highly malignant brain tumor with up to date very poor outcomes often resulting in patient’s death within 1-2 years following diagnosis. Currently, there are no curative treatments for this devastating disease available. Following extensive training in GBM models and establishment of close collaborations with clinical partners such as neurosurgery departments at host and beneficiary locations, within the project several novel drug candidates targeting GBM could be signed and tested for functionality, efficacy and toxicity in vitro and in vivo. Novel online datamining and in-lab biopanning approaches revealed additional potential drug candidates, which might also be suitable candidates targeting GBM.
Data: CORDIS, © European Union
Project objective
Tumours escape proper immune response by propagating immune suppression. Immunotherapy aims to enhance anti-tumour immunity. This highly relevant research area arose recently from advantages in immunology, genetics and oncology. Currently, immunotherapeutics are either protein (e.g. antibodies) or cell-based (e.g. cancer vaccines) and promising approaches target immune checkpoint control, a mechanism crucial for anti-tumour T cell activity.Here, development of a completely new class of immunotherapeutics based on advantageous oligonucleotides is proposed.To this aim, oligonucleotides will be designed to modulate expression of receptor genes involved in immune checkpoint control (e.g. PD-L1, CTLA4) and thus block tumour-mediated T cell inhibition. Of special interest will be the employment of the exon skipping technique to reduce surface receptor and potentially induce antagonistic soluble isoforms.To ensure delivery of oligonucleotides, liposomal or polycationic nanoparticles will be utilized as previous studies demonstrated good tissue bioavailability, e.g. for PTO-antisense RNA and polyethylenimine. Oligonucleotides will be tested for functionality, efficacy and non-toxicity in vitro. To facilitate practical clinical application of the developed drugs, most promising candidates will then be applied to pre-clinical tumour models in vivo. Charmingly, this novel technique will also be applied ex vivo to enhance anti-cancer cell therapy, thus evading systemic distribution.Collaboration of two world-renowned scientific institutions, the German Fraunhofer society and Canadian partner McMaster University, will ensure a prolific environment for successful project conclusion and allow considerable advancement of the career of a most promising European researcher. Furthermore, the project will support development of a key technology in the important field of cancer therapy, thus providing a significant competitive advantage for European interests in health research.
Original text from CORDIS.
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Data: CORDIS, © European Union