Project description
Improving nanobodies’ affinity via chemical mutagenesis
Cancer immunotherapy has emerged as one of the best alternatives to current chemotherapy treatments. Nanobodies (VHH antibodies) are antibodies with a single variable domain located on a heavy chain. Conventional antibodies have VH and VL variable domains, which provide stability and binding specificity. Nanobodies have VHH domains and lack VL domains and occur naturally in camelids and sharks. Nanobodies have found use in such medical fields as oncology, infection and immunity. The EU-funded Chemical Mutagenesis project proposes the development of nanobodies able to recognise HER-2 protein and PD-1 receptors in cancer cells. The objective is to improve the nanobodies’ affinity to their targets using chemical mutagenesis via alanyl radicals, with a goal of resolving the challenges of cancer resistance in the context of immunotherapy.
Objective
Finding a non-aggressive treatment against Cancer is one of the most important challenges that medicine has nowadays. Immunotherapy has emerged as one of the best options to overcome the current problems of chemotherapy. By the use of monoclonal antibodies (mAb), immunotherapy is able to block regulatory checkpoints and, therefore, the immune response against tumoral cells could be modulated.
Trastuzumab, pembrolizumab and nivolumab are some of the mAb approved by the Food and Drug Administration (FDA) for their use against several cancers. Trastuzumab recognizes the overexpressed protein HER2 in breast cancer, whereas the pembrolizumab and the nivolumab recognize the Programmed Cell Death-1 (PD-1) receptor and are used in several cancers such as refractory melanoma.
However, there are reported important issues concerning cancer resistance to these mAb, thus, modifying their characteristics became necessary. Unlike it happens with small molecules, there are several limitations to functionalize an antibody to improve its characteristics. In this context, chemical mutagenesis turns into a powerful tool because it allows the modification of an antibody directly with highly specific chemical reactions, and achieve changes onto its structure that would not be possible by using other techniques such as protein engineering and genetic encoding.
In this proposal I envision the use of nanobodies able to recognize HER-2 protein and PD-1 receptor in order to improve their affinity to their targets by chemical mutagenesis via alanyl radical. The success of this project would provide solutions to the cancer resistance to current immunotherapy.
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 skin cancer melanoma
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology breast cancer
- medical and health sciences basic medicine immunology immunotherapy
- natural sciences chemical sciences
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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-2020
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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.
CB2 1TN CAMBRIDGE
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.