Armoring multifunctional T cells for cancer therapy

Project Information

ARMOR-T

Grant agreement ID: 756017

DOI

10.3030/756017

Project closed

EC signature date 20 September 2017

Start date 1 March 2018

End date 29 February 2024

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 636 710,00

EU contribution

€ 1 636 710,00

Coordinated by

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Germany

Periodic Reporting for period 4 - ARMOR-T (Armoring multifunctional T cells for cancer therapy)

Reporting period: 2022-09-01 to 2024-02-29

Summary of the context and overall objectives of the project

Cellular therapies are the therapeutic use of T cells which have become part of the standard of care in certain blood-borne cancers indications, related to a minority of cancer patients.. From basic studies, it is expected that this type of treatment should be applicable to much more frequent situations and diseases such as solid cancer types. In contrast, clinical studies so far failed to demonstrate activity in these diseases. A major reasons lays in a very different biology between solid and hematological cancers. These key differences have so far been overlooked in cell therapy development. ARMOR-T has taken up the challenge to solve these problems by means of engineering of cells. Such novel therapeutic pipeline has the potential to offer promising treatments to patients suffering from a wide variety of cancer types such as pancreatic, colon or breast cancer. ARMOR-T has a) established novel methods of engineering, b) selected promising engineering combinations and c) tested and characterized such novel strategies. ARMOR-T has layed the basis for further preclinical development and future clinical testing.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

ARMOR-T has set out to validate novel tumor targeting platforms utilizing specific immune cells, so called T cells (such as Karches et al., Clin Can Res 2019 and Stock, JITC 2022). ARMOR-T could also establish a novel technique of genetic modification of T cells to ameliorate tumor tissue recruitment and prove its efficacy in preclinical models (Lesch et al., Nat Biomed Eng 2021 and Cadilha et al., Science Adv. 2021). ARMOR-T has also pioneered a method for identifying novel tumor-associated target structures and design novel receptors against these (such as Gottschlich et al., Nat Biotech 2023 and Märkl et al., Nat Com 2024). These results have been broadly presented at scientific meetings (such as ESMO and ESMO IO) and the most promising candidates are now in further preclinical development towards therapy.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Previous work has mainly focused on effectively targeting the cancer cell and has already led to the approval of gene engineered T cells for distinct indications. The particular biology of non-hematological cancer types has however been mostly disregarded. ARMOR-T has proposed to specifically address said differences through multiple engineering. Such approach has the potential to offer a unique therapeutic avenue for patients suffering from multiple cancer types. ARMOR-T has pioneered novel approaches involving cell engineering and will now progress to developping actual products for future clinical testing and application.

Lytic synapse formation between two T cells and one tumor cell