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NC3Rs | 20 Years: Pioneering Better Science

2022 CRACK IT Challenges announced

T-ALERT and Thyroid Tox Challenge images

Funding of £1.2M is available through this year’s CRACK IT Challenges competition. The two 2022 Challenges encompass animal use in the key areas of endocrine disruption and CAR-T cell therapy.

View the Invitation to Tender (PDF) for more information about the 2022 CRACK IT Challenges competition.

Funding of £1.2M is available through the 2022 CRACK IT Challenges competition* to solve two Challenges identified jointly by the NC3Rs and Sponsors. This annual competition provides UK and EU-based academics and SMEs with the opportunity to apply to develop new 3Rs tools, technologies or approaches and engage with new partners.

The 2022 Challenges encompass animal use in the key areas of endocrine disruption and CAR-T cell therapy. These Challenges have been developed in conjunction with Sponsors who will provide in-kind support and scientific expertise to help solve the Challenge. The aim of these Challenges is to deliver scientific and 3Rs benefits through the development and commercialisation of new products and services that are tailored to end-user needs.

The two Challenges are Sponsored by seven organisations and supported by one Partner. Funding is provided by the NC3Rs and Sponsors will provide in-kind support throughout the Challenges.

The Challenges

Challenge 42 – T-ALERT: Animal-free tumourigenicity assessment of CAR-T and other genetically modified T cells

CAR-T (chimeric antigen receptor-T cell) therapies are emerging as effective therapeutic approaches in the treatment of some cancers. In vivo studies are used to assess the potential for tumourigenicity of these therapies and are invasive and often not predictive of clinical outcome.

This Two Phase Challenge aims to develop an in vitro assay that can reliably evaluate tumourigenicity of human-engineered T cell therapies with the potential to be applied to multiple immune cell types.

3Rs benefitsIn vivo studies to assess tumourigenicity of modified T cells involve a minimum of 30 to 40 immunocompromised mice and can run for up to one year. Development of a predictive in vitro assay has the potential to replace the use of animals.

The Sponsors of this Challenge are Novartis, Takeda, AstraZeneca, Sonomabio, GentiBio.

Challenge 43 – Thyroid Tox: Development of an in silico model to predict thyroid receptor mediated human endocrine disruption

Endocrine disrupting chemicals are found in food, the environment and consumer products and can interact with endocrine related receptors including thyroid receptors. The full effect of these on human health and environmental species is not known.

This Single Phase Challenge aims to develop quantitative structure-activity relationship (QSAR) and molecular docking tools that reliably predict thyroid receptor-mediated human endocrine disruption.

3Rs benefits: The model developed through this Challenge aims to replace the animals used for thyroid receptor related endpoints in regulatory studies, delivering a reduction of 10-15% in the 2,500 animals used per chemical tested.

The Challenge is Sponsored by Shell and Syngenta, the NC3Rs will facilitate access to expert user input on the use of the EPA ToxCast database.

Further information about the CRACK IT Challenges competition process can be found on the NC3Rs Innovation Platform

*Challenges are run using the Small Business Research Initiative (SBRI) provided by Innovate UK (part of UKRI).