Glycans are involved in all biological processes, influencing the functioning of all human cells. Our main goals are to identify glycans as novel therapeutic targets and to contribute to develop innovative immunotherapies to treat patients with cancer and with congenital disorders of Glycosylation (CDG). We aim to understand the fundamental roles of cell surface glycans in modulating the potency of immune cells and their therapeutic potential against infection and cancer. We are also screening aberrant glycosylation that potentiates cancer progression and metastasis, and supresses immune function for targeted therapy. We use state-of-the-art methods: immune-based assays, cell and molecular biology, in vitro and in vivo models and patient cells.
Exploring glycosylation to improve anti-tumor immunotherapy
We developed two technologies that hold promise as therapeutics against cancer. One concerns antibodies against tumor-associated glycans (Loureiro et al, Sci Rep 2018, PCT/IB2016/053901). The sialyl Tn and sialyl Lewis X glycans are aberrantly expressed in cancer and foment evasion from the immune system and capacity for metastasis (Carrascal et al, 2018).
The other technology concerns the modulation of sialylated glycans to enhance the ability of dendritic cells to activate T cells to specifically kill tumor cells (Silva et al, 2016; WO 2017002045 A1). We are currently collaborating with partners to translate our technology into clinics.
A.Human dendritic cells stained with sialic acid-binding lectin (red), B. Colon adenocarcinoma showing sialyl Lewis X expression (brown)
CDG & Allies -PPAIN - Congenital disorders of Glycosylation - Professionals and Patient Associations International Network.
Together with the Portuguese association of CDG (APCDG) we founded an unrivalled international network that joins scientists, physicians, families and patient advocacy groups dedicated to CDG. We are establishing a patient-led unique infrastructure that foments research, awareness and education for CDG (Monticelli et al, 2016; Marques da Silva et al. 2017). Website www.researchcdg. com. CDG & Allies PPAIN is located at FCT NOVA and directed by P. Videira and Vanessa Ferreira.
- “GenMedcare therapeutics research agreement”, Total and Unit funding: €50,000, Paula Videira (PI).
- “Siamab therapeutics research agreement”, Total and Unit funding: €20,000, Paula Videira (PI).
- “GlyCoCan - exploiting glycosylation of colorectal cancer for the development of improved diagnostics and therapeutics”, Total funding: €3,2M and Unit funding: €476,712, Paula Videira (Collaborator).
- “Trifunctional antibodies and dendritic cell-based technologies: a combined approach to cancer immunotherapy” Bluepharma | University of Coimbra Award, Total and Unit funding: €20,000, Paula Videira (PI).
- “ADVANCE - desenvolvimento de novas vacinas anti- cancro a partir de células dendríticas”, FEDER,-QREN, Total funding: €431,012, Unit funding: €215,506 , Paula Videira (co-PI).
Chaves, RP; da Silva, SR; Neto, LGN; Carneiro, RF; da Silva, ALC; Sampaio, AH; de Sousa, BL; Cabral, MG; Videira, PA; Teixeira, EH; Nagano, CS. 2018. Structural characterization of two isolectins from the marine red alga Solieria filiformis (Kutzing) PW Gabrielson and their anticancer effect on MCF-7 breast cancer cells. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 107, DOI: 10.1016/j.ijbiomac.2017.09.116
Araújo, JE; López-Fernández, H; Diniz, MS; Baltazar, PM; Pinheiro, LC; da Silva, FC; Carrascal, M; Videira, P; Santos, HM; Capelo, JL. 2018. Dithiothreitol-based protein equalization technology to unravel biomarkers for bladder cancer. TALANTA, 180, DOI: 10.1016/j.talanta.2017.11.063
Viegas, CSB; Costa, RM; Santos, L; Videira, PA; Silva, Z; Araujo, N; Macedo, AL; Matos, AP; Vermeer, C; Simes, DC. 2017. Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: Implications for calcification-related chronic inflammatory diseases. PLoS One, 12, DOI: 10.1371/journal.pone.0177829
Mariana Silva; Ronald Kam Fai Fung; Conor Brian Donnelly; Paula Alexandra Videira; Robert Sackstein. 2017. Cell-Specific Variation in E-Selectin Ligand Expression among Human Peripheral Blood Mononuclear Cells: Implications for Immunosurveillance and Pathobiology. The Journal of Immunology, 198(9), DOI: 10.4049/jimmunol.1601636
Severino, PF; Silva, M; Carrascal, M; Malagolini, N; Chiricolo, M; Venturi, G; Astolfi, A; Catera, M; Videira, PA; Dall'Olio, F. 2017. Expression of sialyl-Tn sugar antigen in bladder cancer cells affects response to Bacillus Calmette Guerin (BCG) and to oxidative damage. Oncotarget, 8, DOI: 10.18632/oncotarget.17138