Challenges in Antibody Development against Tn and Sialyl-Tn Antigens
Liliana R Loureiro1,2,3, Mylène A Carrascal4, Ana Barbas2
1CEDOC, 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.
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.
Insights
Carbohydrate antigens Tn and sialyl-Tn (STn) are linked to cancer progression but are poorly immunogenic for vaccines. Novel therapeutic antibodies targeting these antigens show promise for cancer treatment.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Tn and sialyl-Tn (STn) carbohydrate antigens are prevalent in carcinomas, correlating with cancer progression and poor prognosis.
- These antigens are associated with an immunosuppressive tumor microenvironment, limiting the efficacy of current therapeutic vaccination strategies.
- Existing anti-Tn and/or STn antibodies have limitations in specificity and efficiency, hindering their clinical application.
Purpose of the Study:
- To review the challenges and opportunities in developing novel therapeutic antibodies targeting Tn and sialyl-Tn (STn) antigens for cancer treatment.
- To explore how advancements in antibody development technologies can overcome the limitations of existing antibodies.
- To highlight the potential of innovative antibody engineering for effective cancer immunotherapy.
Main Methods:
- Review of existing literature on Tn and STn antigens, cancer progression, and antibody development.
- Analysis of various antibody production methodologies, including hybridoma technology, phage display, transgenic mice, and molecular engineering.
- Exploration of novel antibody formats and engineering techniques for enhanced specificity and efficacy.
Main Results:
- Carbohydrate antigens Tn and STn are promising targets for cancer therapy due to their tumor-specific expression.
- Current therapeutic approaches using these antigens have shown limited success due to low immunogenicity.
- Significant advancements in antibody development technologies offer new possibilities for creating effective therapeutic antibodies.
Conclusions:
- Novel therapeutic antibodies targeting Tn and STn antigens are needed to overcome the limitations of current cancer treatments.
- Innovative technologies and engineering techniques are crucial for developing highly specific and efficient antibodies against these tumor-associated antigens.
- The development of such antibodies holds significant potential for advancing cancer immunotherapy and improving patient outcomes.
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