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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Identification and Characterization of Specific Nanobodies against Trop-2 for Tumor Targeting
Yaozhong Hu1, Yi Wang1, Jing Lin1
1Research Institute of Public Health, School of Medicine, Nankai University, Tianjin 300071, China.
Abstract:
Trophoblast cell-surface antigen 2 (Trop-2) is a tumor-associated antigen that is connected with the development of various tumors and has been identified as a promising target for tumor immunotherapy. To date, the immunotherapy against Trop-2 mainly relies on the specific targeting by monoclonal antibody in antibody-drug conjugate (ADC). Alternatively, the single domain antibodies of nanobodies (Nbs) possesses unique properties such as smaller size, better tissue penetration, etc., to make them good candidates for tumor targeting. Thus, it was proposed to develop anti-Trop-2 Nbs for tumor targeting in this study. Generally, three consecutive rounds of bio-panning were performed against immobilized recombinant Trop-2, and yielded three Nbs (Nb60, Nb65, and Nb108). The affinity of selected Nbs was determined in the nanomolar range, especially the good properties of Nb60 were verified as a promising candidate for tumor labeling. The binding to native Trop-2 was confirmed by flow cytometry against tumor cells. The inhibitory effects of the selected Nbs on tumor cell proliferation and migration were confirmed by wound healing and Transwell assay. The clear localization of the selected Nbs on the surface of tumor cells verified the potent labeling efficiency. In conclusion, this study provided several Nbs with the potential to be developed as targeting moiety of drug conjugates.
Insights
Researchers developed novel nanobodies (Nbs) targeting Trophoblast cell-surface antigen 2 (Trop-2) for cancer immunotherapy. These anti-Trop-2 Nbs show high affinity and potential for tumor targeting and drug delivery applications.
Area of Science:
- Oncology
- Immunotherapy
- Biotechnology
Background:
- Trophoblast cell-surface antigen 2 (Trop-2) is a tumor-associated antigen implicated in various cancers.
- Current Trop-2 targeted immunotherapies primarily utilize monoclonal antibodies in antibody-drug conjugates (ADCs).
- Nanobodies (Nbs) offer advantages like smaller size and enhanced tissue penetration for tumor targeting.
Purpose of the Study:
- To develop novel anti-Trop-2 nanobodies (Nbs) for targeted cancer therapy.
- To evaluate the efficacy of these Nbs as targeting moieties for drug conjugates.
Main Methods:
- Three rounds of bio-panning were conducted against immobilized recombinant Trop-2 to select Nbs.
- Selected Nbs (Nb60, Nb65, Nb108) were characterized for affinity, binding to native Trop-2 via flow cytometry, and anti-proliferative/migratory effects using wound healing and Transwell assays.
- Tumor cell surface localization and labeling efficiency were assessed.
Main Results:
- Three anti-Trop-2 Nbs (Nb60, Nb65, Nb108) were successfully generated with nanomolar affinity.
- Nb60 demonstrated promising properties for tumor labeling, with confirmed binding to native Trop-2 on tumor cells.
- Selected Nbs inhibited tumor cell proliferation and migration, and showed potent cell surface labeling efficiency.
Conclusions:
- This study successfully developed anti-Trop-2 nanobodies with significant potential for cancer immunotherapy.
- These Nbs are viable candidates for developing targeted drug conjugates and imaging agents.
- The findings support the advancement of Nbs as a novel therapeutic strategy against Trop-2-expressing tumors.
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