Citation: Dan Li, Haofei Hong, Han Lin, Teng Xu, Zhifang Zhou, Zhimeng Wu. Enhancing tumor-associated carbohydrate antigen vaccine efficacy through synergistic antibody recruitment: A combined strategy targeting TACA heterogeneity[J]. Chinese Chemical Letters, ;2026, 37(5): 111324. doi: 10.1016/j.cclet.2025.111324 shu

Enhancing tumor-associated carbohydrate antigen vaccine efficacy through synergistic antibody recruitment: A combined strategy targeting TACA heterogeneity

The Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China

haofei@jiangnan.edu.cn

zwu@jiangnan.edu.cn

Received Date: 16 February 2025
Revised Date: 12 May 2025
Accepted Date: 14 May 2025
Available Online: 21 May 2025

Figures(5)

Tumor-associated carbohydrate antigen (TACA)-based cancer vaccines face clinical challenges due to heterogeneous TACA expression, which compromises antibody-mediated tumor recognition and leads to suboptimal therapeutic outcomes. To address this limitation, we report a combined strategy that integrates vaccination with TACA-based antibody-recruiting molecules. This approach simultaneously redirects anti-TACA antibodies to tumor cells expressing a secondary target, thereby enhancing the efficacy of TACA-based vaccines. Using sialyl-Tn (sTn) as a model TACA and epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) as model protein targets, we designed two nanobody (Nb)-sTn conjugates as TACA-based antibody-recruiting molecules: EGFR-targeting 7D12-sTn and HER2-targeting C7b-sTn. These conjugates were synthesized via sortase A-mediated ligation and demonstrated strong binding profiles. Importantly, they effectively redirected anti-sTn antibodies, generated by the Theratope vaccine, to target cells in situ, significantly improving the recognition of tumor cells by anti-sTn antibodies. The synergistic potential of these conjugates in amplifying the therapeutic effect of the sTn-KLH vaccine was further validated through complement-dependent cytotoxicity assays. This innovative strategy represents a highly promising approach to overcome the clinical challenges posed by TACA heterogeneity in cancer vaccine development.
- Cancer vaccine,
- Carbohydrates,
- Immunotherapies,
- Nanobody,
- Sialyl-Tn
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