Objective
Many studies have recently archived a remarkable clinical efficacy of immunotherapeutic treatments in several cancers including non-small cell lung cancer (NSCLC). However, these approaches are not always successful and it is currently impossible to predict a therapeutic response or serious adverse event. These fundamental issues need to be addressed and, to recapitulate the complexity of interactions between immune cells and cancer, this has to be done in vivo. However, genetically engineered mouse models (GEMMs) of NSCLC do not mirror the genomic instability and the high mutations rate of their human counterparts. Consequently, these tumours rarely present neo-antigens that can induce an immune response, and are considered poorly immunogenic. To our knowledge, a genetically defined model of an immunogenic spontaneous tumour does not exist. Here, we propose to develop such an immunogenic GEMM (iGEMM).
The leading mouse model of lung cancer is the GEMM Kraslsl-G12D/wtTrp53fl/fl (KP). We propose two strategies to induce either genomic instability or mutation rate in the KP model. 1) We will overexpress Mad2, a component of the mitotic spindle assembly checkpoint, to induce aneuploidy in KP tumours; 2) We will overexpress the cytidine deaminase Apobec3 to increase the mutation rate of KP tumours.
The resulting immunogenic GEMMs (iGEMMs) will be characterised and used to assess new therapies that trigger an immune response and to address mechanisms which drive immunotolerance. iGEMMs will facilitate the investigation of currently available immunotherapies which will help predict clinical response to these therapies and investigation on alternative strategies to treat resistant lung tumours. All together, these investigations will provide novel information regarding the best strategies to cure NSCLC by modulation of the IS.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine oncology prostate cancer
- medical and health sciences clinical medicine oncology lung cancer
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine immunology immunotherapy
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2015
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
NW1 1AT London
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.