Challenges in Antibody Development against Tn and Sialyl-Tn Antigens.
The carbohydrate antigens Tn and sialyl-Tn (STn) are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited success due to their low immunogenicity. Alternatively, anti-Tn and/or STn antibodies may be used to harness the immune system against tumor cells. Whilst the development of antibodies against these antigens had a boost two decades ago for diagnostic use, so far no such antibody entered into clinical trials. Possible limitations are the low specificity and efficiency of existing antibodies and that novel antibodies are still necessary. The vast array of methodologies available today will allow rapid antibody development and novel formats. Following the advent of hybridoma technology, the immortalization of human B cells became a methodology to obtain human monoclonal antibodies with better specificity. Advances in molecular biology including phage display technology for high throughput screening, transgenic mice and more recently molecularly engineered antibodies enhanced the field of antibody production. The development of novel antibodies against Tn and STn taking advantage of innovative technologies and engineering techniques may result in innovative therapeutic antibodies for cancer treatment.
CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, Lisboa 1169-056, Portugal. ab@ibet.pt.|IBET-Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras 2781-901, Portugal. ab@ibet.pt.|IHMT, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Rua da Junqueira 100, Lisboa 1349-008, Portugal. ab@ibet.pt.
Liliana R
LR
Loureiro
CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, Lisboa 1169-056, Portugal. mylene.carrascal@fcm.unl.pt.
Mylène A
MA
Carrascal
IBET-Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras 2781-901, Portugal. ab@ibet.pt.
Ana
A
Barbas
CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, Lisboa 1169-056, Portugal. jose.ramalho@fcm.unl.pt.
José S
JS
Ramalho
CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, Lisboa 1169-056, Portugal. cnovo@ihmt.unl.pt.|IHMT, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Rua da Junqueira 100, Lisboa 1349-008, Portugal. cnovo@ihmt.unl.pt.
Carlos
C
Novo
Structural and Functional Glycobiology Unit, UMR CNRS 8576, University of Lille, Villeneuve d'Ascq 59655, France. philippe.delannoy@univ-lille1.fr.
Philippe
P
Delannoy
CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, Lisboa 1169-056, Portugal. paula.videira@fcm.unl.pt.|Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Caparica 2829-516, Portugal. paula.videira@fcm.unl.pt.
Paula A
PA
Videira
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D005818:Genetic Engineering; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy
D000906:Antibodies; D015295:Antigens, Tumor-Associated, Carbohydrate; C040286:Tn antigen; C055491:sialosyl-Tn antigen
Sialyl Tn antigen; Tn antigen; antibody production; immune response; therapeutic antibodies