Objective
The development of monoclonal antibodies (mAb) to target tumor cells has tremendously improve cancer immunotherapy and benefit the treatment of aggressive cancer such as some types of lymphomas, leukemias, multiple myeloma and metastatic cancers. One of the mechanisms of action is the induction of antibody-dependent cellular cytotoxicty (ADCC) through the activation of CD16 on NK cells after binding to the Fc portion of Ab-coated tumor cells. Therefore, strategies that combine NK cell activation and mAb therapy has been intensively explored. However, tumor heterogeneity and unstable expression of the targeted molecule in the tumor cells limits ADCC for mAb therapy resulting in cancer relapse. Furthermore, intrinsic NK immunregulatory mechanisms as well as NK-specific tumor evasion mechanisms have also negatively impacted the use of NK cell-based therapies. In this proposal we will explore the mechanisms involved in the reduced NK cell function (NCF) observed after ADCC and/or NK cell activation (NCA) in order to develop novel strategies to achieve a sustained and stronger NCF by combining stimulating signals with suppression of inhibitory signals such as costimulation via CD137 and IL12, or SHP1/2 blockade. We hypothesize that the adoptive transfer (AT) of NK cells expanded by this novel method will result in better anti-tumor responses after mAb therapy even in tumor cells that express limited amount of the target molecule and limiting consequently cancer relapse rates. Furthermore, due to the overall improvement on NCF, we expect that the combination of AT NK cells with hematopoietic stem cell transplantation (HSCT) will also increase anti-tumor responses; which efficacy up to date has shown to be rather limited. Given the versatility of our approach, this therapy can be used for the treatment of many cancers, but particularly hematological and metastatic cancers and potentially can be translated into the clinic in a short time frame.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine oncology skin cancer melanoma
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology colorectal cancer
- medical and health sciences basic medicine immunology immunotherapy
- medical and health sciences clinical medicine oncology leukemia
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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 - Marie Skłodowska-Curie Individual Fellowships (IF)
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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-2016
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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.
31008 Pamplona
Spain
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.