In vivo immunotherapy of lung cancer using cross-species reactive vascular endothelial growth factor nanobodies
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Fatemeh Kazemi-Lomedasht1, Kamran Pooshang-Bagheri1, Mahdi Habibi-Anbouhi2
1Biotechnology Research Center, Biotechnology Department, Venom & Biotherapeutics Molecules Lab., Pasteur Institute of Iran, Tehran, Iran.
Objectives:
Lung cancer is the main leading cause of cancer death worldwide. Angiogenesis is the main step in proliferation and spreading of tumor cells. Targeting vascular endothelial growth factor (VEGF) is an effective approach for inhibition of cancer angiogenesis. Nanobodies (NBs) are a novel class of antibodies derived from the camel. Unique characteristics of Nbs like their small size and good penetration to tumor tissues makes them promising tools in drug development. Development of NBs targeting both human and mouse VEGF is required for understanding their in vivo functions. Therefore, development of cross-species reactive anti-VEGF Nbs for immunotherapy of lung cancer was the main aim of the current study.
Materials And Methods:
Here we developed NBs from Camelus dromedarius library with high specificity and binding affinity to both human and mouse VEGF. In vitro and In vivo function of developed NB was evaluated on human endothelial cells and lung epithelial tumor cells (TC-1).
Results:
A nanobody showed the highest affinity to human and mouse VEGF and potently inhibited VEGF in the ELISA experiment. Anti-VEGF NBs significantly inhibited in vitro human endothelial cell migration through blockade of VEGF (P=0.045). Anti-VEGF NBs also significantly inhibited in vivo TC-1 growth in a dose-dependent manner (P=0.001) and resulted in higher survival rate in the nanobody treated group.
Conclusion:
These findings demonstrate the potential of anti-VEGF NBs in tumor growth inhibition and are promising as novel cancer therapeutic candidate.
Insights
Researchers developed novel nanobodies targeting vascular endothelial growth factor (VEGF) to inhibit lung cancer growth. These nanobodies effectively reduced tumor cell proliferation and increased survival rates in preclinical models, showing promise for cancer immunotherapy.
Area of Science:
- Immunology and Cancer Research
- Biotechnology and Drug Development
Background:
- Lung cancer is a leading cause of cancer mortality globally.
- Tumor angiogenesis, driven by vascular endothelial growth factor (VEGF), is crucial for cancer progression.
- Nanobodies (NBs) offer potential therapeutic advantages due to their small size and tumor penetration.
Purpose of the Study:
- To develop cross-species reactive anti-VEGF nanobodies (NBs) for lung cancer immunotherapy.
- To target both human and mouse VEGF for comprehensive in vivo studies.
- To evaluate the therapeutic potential of anti-VEGF NBs in preclinical lung cancer models.
Main Methods:
- Development of specific nanobodies (NBs) targeting human and mouse VEGF from a Camelus dromedarius library.
- In vitro evaluation of NB efficacy on human endothelial cells and lung epithelial tumor cells (TC-1).
- In vivo assessment of NB anti-tumor activity and survival impact in a TC-1 mouse model.
Main Results:
- A selected nanobody demonstrated high affinity for both human and mouse VEGF, potently inhibiting VEGF activity in ELISA.
- Anti-VEGF NBs significantly inhibited in vitro endothelial cell migration by blocking VEGF (P=0.045).
- In vivo administration of anti-VEGF NBs resulted in dose-dependent inhibition of TC-1 tumor growth (P=0.001) and improved survival rates.
Conclusions:
- Developed anti-VEGF nanobodies show significant potential for inhibiting tumor growth.
- These NBs represent promising novel therapeutic candidates for cancer immunotherapy.
- The cross-species reactivity facilitates further in vivo research and therapeutic development.
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