Glycobiology and Tumor Immunology
Proteins and carbohydrates (sugars) interaction plays an essential role in several cellular processes, such as cell proliferation and differentiation, as well as in different diseases, including viruses, bacteria and parasites infections. To perform these specialized functions, some types of carbohydrates bind to proteins creating complex structures called glycoproteins, which are found on the surface of cells and which influence cellular communication. Glycobiology is a discipline that studies the structure and function of carbohydrates as entities linked to cell function.
Our laboratory is focused on the identification and study of some alterations of glycosylation in cancer. Altered glycosylation produces some structures that are tumour-specific. Against them, we generate different types of biotechnological developments in view of their biomedical application. Our lines of research are oriented to understand characteristics of tumour biology and, especially, to develop new molecular procedures in view of their application to the diagnosis and treatment of the disease.
Image: Human colon cancer identified by anti-Trypanosoma cruzi antibodies. Left: Malignant colon tumour (positive).Right: Adjacent normal colonic mucosa (negative).
On biopharmaceuticals, the focus of study of the laboratory, we have developed specific kits and analytical methodologies base on requests from productive sector. Some of the projects that we are working on are:
Anti-TN antibody engineering in molecular imaging and cancer immunotherapy.
Using different recombinant antibodies and fragments of them, we found that the Tn antigen is a molecular target of interest for the diagnosis and treatment of human tumours. We develop fragments of antibodies (scfv, minibodies and nanobodies) for their application in molecular imaging. We also investigated the development of immuno-nanoparticles to direct drugs towards tumours.
O-glycosylation enzymes as predictive and predictive biomarkers in oncology.
We evaluated whether the expression of GalNAc-Ts enzymes, which catalyse the first stage of O-glycosylation, can influence the biological properties of cancer cells (invasiveness, chemo-resistance, etc.), to subsequently develop useful diagnostic procedures in clinical oncology.
Anti-tumour immunotherapy using parasite molecules.
We found that some cancer-specific glyco-antigens are also expressed in certain parasites. We observed that immunization with extracts of Trypanosoma cruzi and Echinococcus granulosus induces anti-tumour immune responses in animal models. We seek to elucidate the molecular and cellular bases of this type of immune responses in order to generate a new type of anti-tumour therapeutic strategy.
- International course “Glycobiology and Cancer: from Chemistry to Clinical applications”.
Nov 29–Dec 7, 2013. Organisers: Eduardo Osinaga and Nora Berois.
- International course “Progress in Molecular oncology and its clinical impact”. May 2-6, 2016. Organisers: Eduardo Osinaga, Nora Berois and Mario Varangot.
- International course “Progress in Molecular oncology and its clinical impact”. Nov 27- Dec 1, 2017. Organisers: Eduardo Osinaga, Nora Berois, Luis Ubillos and Gabriel Krygier.
- Hubert-Haddad P, Amigorena S, Sastre-Garau X, Osinaga E, Pritsch O, Oppezzo P, Perez F, Moutel S. An antibody specific for the Tn antigen for the treatment of cancer.
European Patent WO/2009/007222 (2009)
2023-2024 – “Development of a liquid biopsy procedure for assessment of response to immunotherapy in cancer”. Funded by: Fondo Sectorial de Salud, ANII, Uruguay. Responsible: Eduardo Osinaga.
2022-2024 – “Application of genetic engineering to enhance the anti-tumour activity of a cancer-specific antibody”. Funded by: Fondo María Viñas, ANII, Uruguay. Responsible: Eduardo Osinaga.
2018-2022 – “Cancer immunotherapy using parasite molecules”. Funded by: Fondo María Viñas, ANII, Uruguay. Responsible: Eduardo Osinaga.
2018-2020 – “Cancer immunotherapy using molecules of Trypanosoma cruzi”. Funded by: ANII-GSK. Responsible: Eduardo Osinaga.
2016-2017 – “Immune-nanoparticles in cancer treatment Project”.
Responsibles: Eduardo Osinaga and Alvaro Mombrú.
“Linking qualified diaspora with intensive sectors in knowledge, technology and innovation of Uruguay”. BID-MIEM Project. ATN/KF-13883-UR
2015-2019 – “Immunity and cancer”. Funded by: Programa Grupos de Investigación, CSIC-UdelaR, Uruguay. Responsible: Eduardo Osinaga.
2015-2018 – “Cancer molecular imaging with anti-Tn tumour antigen antibodies produced by genetic engineering”. Responsible: Eduardo Osinaga. ANII I+I (co-funded by: De Larrobla y asociados).
- Berois N, Pittini A, Osinaga E. Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives. Cancers. 2022; 14(3):645. https://doi.org/10.3390/cancers14030645
- Olano C, López V, Freire T, Rodríguez X, Pontet Y, Alemán A, Rodríguez N, Rovira L, Trucco E, Osinaga E, Cohen H, Quigley EM. Irritable bowel syndrome in celiac disease – relationships to celiac disease antibodies and levels of pro-inflammatory cytokines. Rev Gastroenterol Peru. 2020; 40:127-135
- Ubillos L, Berriel E, Mazal D, Victoria S, Barrios E, Osinaga E, Berois N. Polypeptide-GalNAc-T6 expression predicts better overall survival in patients with colon cancer. Oncol Lett. 16:225-234 (2018).
- Festari MF, Trajtenberg F, Berois N, Pantano S, Revoredo L, Kong Y, Solari-Saquieres P, Narimatsu Y, Freire T, Bay S, Robello C, Bénard J, Gerken TA, Clausen H, Osinaga E. Revisiting the human polypeptide GalNAc-T1 and T13 paralogs. Glycobiology 27:140-153 (2017).
- Berois N, Touya D, Ubillos L, Bertoni B, Osinaga E, Varangot M. Prevalence of EGFR mutations in lung cancer in Uruguayan population. Journal of Cancer Epidemiology ID 6170290 (2017).
- Nozar F, Greif D, Franciulli A, Barrios E, Osinaga E, Berois N. Prevalence and Distribution of High-Risk Human Papillomavirus Genotypes in Invasive Carcinoma of the Uterine Cervix in Uruguay. An update on clinical outcome. Medical Research Archives. Volume 5, issue 5. May (2017).
- Sedlik C, Heitzmann A, Viel S, Ait Sarkouh R, Batisse C, Schmidt F, De La Rochere P, Amzallag N, Osinaga E, Oppezzo P, Pritsch O, Sastre-Garau X, Hubert P, Amigorena S, Piaggio E. Effective antitumor therapy based on a novel antibody-drug conjugate targeting the Tn carbohydrate antigen. Oncoimmunology. 5:e1171434 (2016).
- Osinaga E, Freire T, Ubillos L. Author’s reply to: Could cross-immunological reactivity to Trypanosoma cruzi antigens be considered a rational strategy for designing vaccines against cancer? Int J Cancer. 139:2144 (2016).
- García E, Tiscornia I, Libisch G, Trajtenberg F, Bollati-Fogolín M, Rodríguez E, Noya V, Chiale C, Brossard N, Robello C, Santiñaque F, Folle G, Osinaga E and Freire T. MUC5B silencing reduces chemo-resistance of MCF-7 breast tumor cells and impairs maturation of dendritic cells. Int. J. Oncol. 48:2113-23 (2016).
- Ubillos L, Freire T, Berriel E, Chiribao ML, Chiale C, Festari MF, Medeiros A, Mazal D, Rondán M, Bollati-Fogolín M, Rabinovich GA, Robello C and Osinaga E. Trypanosoma cruzi extracts elicits protective immune response against chemically-induced colon and mammary cancers. Int J Cancer 138:1719-31 (2016).
- Ikemori R, Longo Machado C, Furuzawa K, Nonogaki S, Osinaga E, Umezawa K, Carvalho MA, Verinaud L and Chammas R. Galectin-3 up-regulation in hypoxic and nutrient deprived microenvironments promotes cell survival. Plos One 4;9(11):e111592 (2014).
- Berois N and Osinaga E. Glycobiology of neuroblastoma: Impact on tumor behavior, prognosis and therapeutic strategies. Frontiers in Oncology 4:114 (2014).
- Libisch G, Casás M, Chiribao ML, Moreno P, Cayota A, Osinaga E, Oppezzo P and Robello C. GalNAc-T11 as a potential new molecular marker in chronic lymphocytic leukemia. Gene 533:270-9 (2014).
- Berois N, Heard I, Fort Z, Alonso R, Sica A, Moerzinger P, Rodriguez G, Sancho-Garnier H, Osinaga E and Favre M. Prevalence of type-specific HPV infection in Uruguay. J. Med. Virol. 86:647-52 (2014).
- Berriel E, Russo S, Monin L, Festari MF, Berois N, Fernández G, Freire T and Osinaga E. Anti-tumor activity of human hydatid cyst fluid in a murine model of colon cancer. The Scientific World Journal 2013:230176 (2013).
- Noya V, Bay S, Festari MF, García E, Rodriguez E, Chiale C, Ganneau C, Baleux F, Astrada S, Bollati –Fogolín M, Osinaga E and Freire T. Mucin-like peptides from Echinococcus granulosus induce antitumor activity. Int. J. Oncology 43:775-84 (2013).
- Mazal D, Lo-Man R, Bay S, Pritsch O, Dériaud E, Ganneau C, Medeiros A, Ubillos L, Obal G, Berois N, Bollati-Fogolin M, Leclerc C and Osinaga E. Monoclonal antibodies toward different Tn-amino acid backbones display distinct recognition patterns on human cancer cells. Implications for effective immuno-targeting of cancer. Cancer Immunol. Immunother. 62:1107-22 (2013).
- Berois N, De Cremoux P, Mazal D, Sica A, Cedeira M, Caserta B, Barrios E, Osinaga E and Sastre-Garau X. Prevalence and distribution of high-risk human papillomavirus genotypes in invasive carcinoma of the uterine cervix in Uruguay. Int. J. Gynecol. Cancer 23:527-532 (2013).
- Dalotto-Moreno T, Croci DO, Cerliani JP, Martinez-Allo VC, Dergan-Dylon S, Mendez Huergo SP, Stupirski JC, Mazal D, Osinaga E, Toscano MA, Sundblad V, Rabinovich GA, Salatino M. Targeting galectin-1 overcomes breast cancer associated immunosuppression and prevents metastatic disease. Cancer Res. 73:1107-17 (2013).
- Berois N, Gattolliat C-H, Barrios E, Capandeguy L, Douc-Rasy S, Valteau-Couanet D, Bénard J and Osinaga, E. GALNT9 gene expression is a prognostic marker in neuroblastoma patients. Clinical Chemistry 59:225-233 (2013).
- Medeiros A, Berois N, Incerti M, Bay S, Franco Fraguas L and Osinaga E. A Tn antigen binding lectin from Myrsine coriacea displays toxicity on human cancer cell lines. J Natural Med 67:247-54 (2013).
- Freire T and Osinaga E. The sweet-side of cancer immunotherapy. Immunotherapy; 4:719-34 (2012).
- Chiribao M, Libisch G, Osinaga E, Parodi A and Robello C. Cloning, localization and differential expression of the Trypanosoma cruzi TcOGNT-2 glycosyltransferase gene. Gene 498:147-54 (2012).
- Hubert P, Heitzmann A, Viel S, Nicolas A, Sastre-Garau X, Oppezzo P, Pritsch O, Osinaga E and Amigorena S. Antibody-dependent cell cytotoxicity synapses form in mice during tumor-specific antibody immunotherapy. Cancer Research 71:5134-43 (2011).
- Hill M, Mazal D, Biron V, Pereira L, Ubillos L, Berriel E, Ahmed H, Freire T, Rondán M, Vasta GR, Liu FT, Iglesias MM and Osinaga E. A novel clinically-relevant animal model to study galectin-3 and its ligands during colon carcinogenesis. J. Histochem. Cytochem. 58:553-65 (2010).
- Robles A, Medeiros A, Berois N, Balter H, Pauwels E and Osinaga E. In site interaction evaluation of Tn density by inhibition/competition assays. Nuclear Medicine and Biology 37:453-8 (2010).
- Gomes J, Marcos NT, Berois N, Osinaga E, Magalhães A, Pinto-de-Sousa J, Almeida R, Gärtner F and Reis CA. Expression of UDP-N-acetyl-D-galactosamine: Polypeptide N-acetylgalactosaminyltransferase-6 in gastric mucosa, intestinal metaplasia, and gastric carcinoma. J. Histochem. Cytochem. 57:79-86 (2009).
- Croci D, Cognoa I, Rumie Vittara N, Salvatierra E, Trajtenberg F, Podhajcer O, Osinaga E, Rabinovich G and Rivarola V. Silencing survivin gene expression promotes apoptosis of human breast cancer cells through a caspase-independent pathway. J. Cell. Biochem. 105:381-90 (2008).
- Medeiros A, Chiribao ML, Ubillos L, Festari MF, Saldaña J, Robello C, Domínguez L, Calvete JJ and Osinaga E. Mucin-type O-glycosylation in Mesocestoides vogae (syn. corti). Int. J. Parasitology 38:265-76 (2008).
- Osinaga E. Expression of cancer-associated simple mucin-type O-glycosylated antigens in parasites. Critical review. IUBMB Life 59:269-73 (2007).