Since its inception, the Unit's activity has focused on the study of tumour angiogenesis and its inhibition as a therapeutic strategy, having developed antiangiogenic antibodies with antitumour effect in vitro and in vivo, in vivo models of human angiogenesis for validating these agents, based on tissue engineering and molecular imaging techniques, and large-scale screening systems for testing compounds with antiangiogenic potential, which have generated numerous original publications. In recent years, without abandoning angiogenesis, the group has become interested in supporting mural cells, specifically pericytes that line the endothelial cells of the microvasculature. These cells, previously attributed a purely structural role, have gained great prominence from a functional standpoint, not only in angiogenesis but also in other novel areas. Specifically, we have described for the first time their involvement in the inflammatory response to LPS, and we have as yet unpublished data on their role in the tumour microenvironment through the production of soluble factors that promote the proliferation, migration and chemotherapy resistance of tumour cells.

All of this without losing sight of the patient's perspective, which is the ultimate goal of our work. For this reason, we have also sought to translate our molecular-level knowledge into clinical practice. To this end, we have the collaboration of the Medical Oncology Department, which conveyed to us its interest in identifying predictive biomarkers of response to antiangiogenic treatment with the anti-VEGF monoclonal antibody bevacizumab in patients with colorectal cancer, a project funded by the ISCIII. By analysing the transcriptome of tumours from responding and non-responding patients, we managed to identify a gene whose overexpression determines resistance to treatment. Within this line of research, it should also be noted that the PI has been part of the Angiobodies 2.0 consortium funded by the CAM, aimed at developing recombinant antibodies against the endothelium for therapeutic and diagnostic use, in which groups from the CNIO, CNIC, CNB and UAM took part, with whom we continue to collaborate. Part of the consortium's activities included organising the International Symposia “Of vessels and blood cells: recent advances in angiogenesis” (2010) and “Targeting tumor angiogenesis with antibody-based technologies” (2015).

Because it should not be forgotten that the group's other line of work is antibody engineering, which has given rise to a spin-off in which we take part as an academic group in Retos-Colaboración and CDTI projects. In 2001, the PI published as first author the original article “Generation and characterization of recombinant human antibodies specific for native laminin epitopes: potential application in cancer therapy”, and since then more than 30 publications, including original articles and reviews, have been produced in this field. This work has included the selection of recombinant antibody libraries in scFv format expressed on the surface of phages, both in vitro and in vivo; the design, expression and purification of recombinant antibodies in different formats (diabody, trimerbody, BiTE, LiTE, TriTE, ATTACK), some of them original to us and patent-protected; their structural and functional characterisation in vitro and the demonstration of their therapeutic effect in vivo. We have also used gene therapy strategies for the in vivo expression of these antibodies using cells modified ex vivo with lentiviral vectors. Current projects aim to generate bispecific immunostimulatory antibodies for the treatment of different types of cancer, allowing effector T cells to be activated not non-specifically but within the tumour microenvironment. In vivo trials are underway to test the therapeutic efficacy of both the human and murine versions.

Finally, it should be mentioned that we maintain collaborations with groups from the Universidad Complutense de Madrid and the Universidad de Zaragoza for the production of immunotoxins formed by the genetic fusion of a recombinant antibody and a cytotoxic protein. As a result of the latter, a patent is being drawn up to protect the intellectual property of the invention, of which FIBHUPH is a co-holder.