Innovation Associate for highly specific Tumour Associated Carbohydrate Antigens

Project Information

InnoTACA

Grant agreement ID: 957090

DOI

10.3030/957090

Project closed

EC signature date 15 September 2020

Start date 1 February 2021

End date 30 April 2022

Funded under

• INDUSTRIAL LEADERSHIP - Innovation In SMEs

Total cost

No data

EU contribution

€ 100 075,00

Coordinated by

CELLMABS SA
Portugal

Periodic Reporting for period 1 - InnoTACA (Innovation Associate for highly specific Tumour Associated Carbohydrate Antigens)

Reporting period: 2021-02-01 to 2022-04-30

Summary of the context and overall objectives of the project

Cancers such as colorectal cancer (CRC) have very poor standard of care and thus own an unmet need for reliable and specific target. CRC is a major cause of the cancer burden worldwide with approximately 1.4 million cases in 2012 and approximately 700,000 annual deaths, especially when advanced and unresectable. In addition to the severe medical and quality-of-life consequences for patients and their families, CRC has far-reaching effects on healthcare system and economy, reaching total costs of 13.1 billion euros within Europe in 2009. Treatment is only efficient at early stages, and there is still an unmet need for better therapeutic and diagnostic targets for major breakthroughs in treatment. In spite of new and improved genomic and proteomic technologies, it hasn’t been possible to identify CRC-specific therapeutic targets that are able to reliably and accurately predict cancer outcomes.
InnoTACA addresses these unmet needs by hiring an Innovation Associate, expert on groundbreaking technology to innovate tumour associated carbohydrate antigen (TACA) discovery to apply in cancer theranostic. It combines high-quality transferable-skill training with excellent scientific training in glycobiology and with regard to CRC. InnoTACA has contributed to identify and validate highly specific TACAs which would serve as a lead for the development of safer and more cost-effective immunotherapies, even for advanced unresectable CRC tumours. Such immunotherapies will provide the CellmAbs improved products to capitalize and compete with current healthcare business.
The InnoTACA objectives were:
1-Development and implementation of the InnoTACA Training programme, including business and innovation skills development within the context of the innovation idea.
2- Integration of the InnoTACA Associate in CellmAbs.
3- To identify novel TACA targets for antibody and T cell-based cancer immunotherapy
4- To ensure efficient and timely management and coordination of the InnoTACA project.

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

The work carried out during the reporting period of the InnoTACA project is in line with Annex 1 of the Grant Agreement. The InnoTACA project aimed to address the unmet need for specific therapeutic targets, that can reliably and accurately predict cancer outcomes, by hiring an Innovation Associate. The Associate contracted, Mariangela Natale, is an expert on groundbreaking technology that allows CellmAbs to boost the discovery of Tumour-Associated Carbohydrate Antigen (TACA) to apply in cancer theranostic.
The project combined training in high-quality transferable skills in glycobiology, to select specific TACAs. The identified TACAs were then used as target leads for developing antibody-related immunotherapies. Such immunotherapies will provide the CellmAbs with safer and more cost-effective products than existing anti-cancer therapies. These requisites are essential for CellmAbs to capitalize and compete with the current healthcare business.
The project had three main work packages (WP) to fulfil our objectives, the WP1 Training programme and integration, WP2 Development of the innovation project by the Associate and WP3 Project Management, as detailed below.


We accomplished the milestones and reported all the deliverables we committed ourselves to at InnoTACA. We were able to deliver a Tailored training plan (Deliverable (D)1.1); Integrate the Associate in CellmAbs (D1.2); Implement the tailored training (D1.3); Report describing the development of the innovation project (D2.1); Report on data protection and data management (D3.1 D3.2 and D3.3); and Reports on ethic requirements (D4.1 D4.2 D4.3 D4.5). Deviations and amendments are included in this report.

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)

At present, there is still no efficient biomarker capable of providing cancer specificity and safety when used as a target. Current immunotherapeutics still have patients who do not respond or show considerable toxicity. Toxicity presents life-threatening risks and costs and low quality of life. For that reason, the current standard of care for cancers continues to be chemotherapy, which often fails to provide significant clinical benefits. The technology brought by the InnoTACA Associate is based on sialyl Tn (STn) antigen. The STn is a short, sialylated O-glycan antigen not expressed in healthy cells and associated with cancer. STn expression has been described in various epithelial cancers, including colorectal cancer. The Associate has used immunohistochemistry analysis and showed that almost all epithelial cancers tumours and corresponding metastasis express STn, but at different intensities. STn is correlated with poor prognosis and reduced survival and has pathogenic implications, promoting cell migration, positive oncogenic signalling, epithelial-mesenchymal transition and stemness.
STn is a post-translational modification of cell surface proteins, including those already used as cancer biomarkers such as mucins. Yet, since STn is not observed in healthy tissue, it makes it a unique and reliable cancer biomarker.
STn has been shown to act as an immune checkpoint hampering immune activation. Yet, in contrast to other immune checkpoints targets of immunotherapies, STn is not critical for the normal function of the immune response. Therefore targeting STn is not expected to lead to essential side effects, as observed with other immune checkpoints such as PD-1 /PD-L1 axis.

The Associate has not only validated STn as a unique TACAs, but she was also involved in the development of novel high-affinity antibody variants against STn. These antibody variants are unique and different from the antibodies licensed to CellmAbs. She, together with the CellmAbs team, tested the new variants in vitro and in vivo as single agents (pipeline 1), adoptive T cell therapies (pipeline 2), antibody-drug conjugate (pipeline 3) and bispecific antibodies (pipeline 4). Therefore the Associate has been allowed to take advantage of existing pipelines of CellmAbs, and develop new distinct pipelines.
The InnoTACA project through the Associate has allowed the CellmAbs team to improve their technological and scientific expertise in developing immuno-oncology agents. This expertise has been internationally recognized, as shown by CellmAbs capacity to attract funding from venture capitals (Portugal Ventures, Bionova Capital), scientific foundations (Portuguese Foundation for Science and Technology), and H2020 (the present call), thus warranting around 2 Million euros funding for the following years. Furthermore, CellmAbs has attracted interest from several renowned scientists and international experts in glycoimmunology and oncology and allowed the establishment of several partnerships and collaborations with national and international research and medical institutes in 2021. Namely with Instituto Portugues de Oncologia, Champalimaud Foundation, Pennsylvania University, Centre for Energy, Environment and Technology (CIEMAT), Spain.
InnoTACA has promoted professional development by encouraging the Associate and the other employees to listen to knowledgeable speakers at symposiums or relevant events. In particular, she attended the following webinars and successfully completed the relative webinar exam session.

Cancer cells are covered by aberrant sugars, being targeted by antibodies