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.
