Project description
Caged innate immune activator in preclinical cancer models
Immune therapies have revolutionised the treatment of melanoma and leukaemia, but they have not been effective for all cancers due to the presence of suppressive immune cell types in tumours. Chemically blocked innate immune activators that can be reactivated locally have been developed, offering a potentially safe and powerful option. The ERC-funded TIGER project will assess the effectiveness of the first caged innate immune activator in a preclinical cancer model, verifying its strength, pharmacokinetics, and caging/decaging behaviour. The project will expand the range of innate activators, antibodies, and uncaging chemistries that can be used. Additionally, it will conduct market research to identify the best combination of tumour-immune activator-antibody for further clinical development.
Objective
Immune therapies have caused a paradigm shift in the treatment of melanoma and leukemias. However, the broad Immune therapies have caused a paradigm shift in the treatment of melanoma and leukemias. However, the broad application of these immune therapies to all cancers has not worked. One of the major reason for this failure is the presence of innate immune suppressive cell types in many tumour types, such as macrophages, NK-, dendritic, and myeloid cells. Tumour selective reactivation of these cells is considered one of the holy grails for the future of immune therapy.
Most endeavours in achieving this are severely hampered by the toxicity of innate immune activators: they cause strong off-site-on-target systemic immune activation, which can lead sepsis-like symptoms and death. Developing innate immune activating therapies that are both powerful and safe are therefore key to applying immune therapies across the cancer landscape.
As part of my ERC-CoG-Grant I have developed innnate immune activators that are chemically blocked, but that can be reactivated locally to offer. This approach can potentially serve as exactly the safe and potent innate activator required. By targeting the innate activators to the tumour and only activating them once they have accumulated there, we can decouple the therapeutic activity from the systemic toxicity that plagues these approaches.
In this proposal, we aim to evaluate the first such a caged innate immune activator in a pre-clinical cancer model. We will validate its potency, pharmacokinetics and caging/decaging behaviour. In addition, we will broaden the scope of the innate activators, antibodies and uncaging chemistries that can be applied. We will also perform market research to determine the optimal tumour-immune activator-antibody combination to take forward into clinical development and begin to take the necessary steps to spin out a company based on this work to bring these non-toxic innate activators to the clinic.
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
- medical and health sciences basic medicine pharmacology and pharmacy pharmacokinetics
- medical and health sciences clinical medicine oncology leukemia
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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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HORIZON.1.1 - European Research Council (ERC)
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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
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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.
HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-POC
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2311 EZ Leiden
Netherlands
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