Abstract
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.
Highlights
The deranged expression of glycans is a hallmark of cancer
We have observed that blockade of STn antigens expressed by cancer cells was able to lower the induction of tolerance in vitro and dendritic cells (DCs) become more mature [66]. These findings suggest that targeted therapies based on antibodies may provide efficient means to enhance immune responses against STn tumor cells
The market for therapeutic antibodies has been growing significantly within the healthcare industry so that 40 years after the generation of the first monoclonal antibody [72], around 47 recombinant monoclonal antibody products have been approved in the United States or Europe for the treatment of a wide variety of diseases, ranging from cancer to infectious and cardiovascular diseases to autoimmune diseases [73,74]
Summary
The deranged expression of glycans is a hallmark of cancer Glycans such as the Thomsen-Friedenreich related antigens, Tn and sialyl-Tn (STn), show a very tumor specific pattern and, in most cancers, they are associated with disease progression and patient’s response to treatment. These antigens have triggered enthusiasm among the scientific community as diagnostic and prognostic biomarkers. The antibodies developed against these antigens have been mainly regarded as tools for diagnosis and prognosis The exploitation of these antibodies as immunotherapeutic tools to elicit anti-tumor immune responses has been completely disregarded. A portfolio of cutting edge methodology is here described that can be used to speed the production of more effective antibodies or novel engineered antibody-based molecules as innovative immunotherapies against STn or Tn
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