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Published on: May 4, 2017
In vitro and in vivo evaluation of a humanized anti-APRIL antibody
1Laboratory of the Animal Center, Academy of Military Medical Sciences, No. 27 Taiping Road, Haidian District, Beijing 100850, China. gaoquansheng2002@yahoo.com.cn
Abstract:
A proliferation-inducing ligand (APRIL) is overexpressed in many cancers such as colorectal, gastric and liver. Silence APRIL gene or neutralize its expression may serve as therapeutic strategies to manage those cancers. Current phase I clinical trial shows that heavily pretreated patients were well tolerated high dose intravenous infusion. Herein, we report a humanized antibody (Ab) that neutralizes APRIL protein and inhibits cancer cell proliferation both in vitro and in vivo. The Ab was generated through conjugating foreign immunodominant T-helper cell (Th) epitopes to the N- or C-terminal of four soluble APRIL mutants. In vitro anti-proliferation effects were evaluated in both Raji and Jurkat cell lines. In vivo inhibition of tumor growth was determined in a tumor xenograft animal model with green fluorescent protein (GFP) positive Raji cell line. In vitro data demonstrated that this Ab significantly inhibited both Raji and Jurkat cell proliferation in a dose-dependent manner. The molecular imaging data demonstrated in vivo tumor growth delay when animals were treated with Ab. In conclusion, we have developed a humanized anti-APRIL Ab, which is effective in inhibiting tumor cell proliferations both in vitro and vivo. The humanized Ab has potential to reduce the immunoresponse in the clinical situation. This Ab also can be used in other APRIL mediated diseases such as Sjogren syndrome, multiple sclerosis and systemic lupus erythematosus.
Insights
A novel humanized antibody effectively neutralizes proliferation-inducing ligand (APRIL), inhibiting cancer cell growth in vitro and in vivo. This antibody shows promise for treating cancers and other APRIL-mediated diseases.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- APRIL is overexpressed in various cancers, including colorectal, gastric, and liver cancers.
- Targeting APRIL presents a potential therapeutic strategy for managing these malignancies.
- A humanized antibody (Ab) was developed to neutralize APRIL protein and inhibit cancer cell proliferation.
Purpose of the Study:
- To develop and evaluate a humanized antibody that neutralizes APRIL.
- To assess the in vitro and in vivo efficacy of the anti-APRIL antibody in inhibiting cancer cell proliferation and tumor growth.
Main Methods:
- The humanized antibody was generated by conjugating T-helper cell epitopes to soluble APRIL mutants.
- In vitro anti-proliferation effects were tested on Raji and Jurkat cell lines.
- In vivo tumor growth inhibition was assessed using a tumor xenograft animal model with GFP-positive Raji cells.
Main Results:
- The antibody demonstrated significant dose-dependent inhibition of Raji and Jurkat cell proliferation in vitro.
- Molecular imaging revealed in vivo tumor growth delay in animals treated with the antibody.
- The humanized antibody effectively inhibits tumor cell proliferation both in vitro and in vivo.
Conclusions:
- A humanized anti-APRIL antibody has been successfully developed.
- This antibody is effective in inhibiting cancer cell proliferation and tumor growth.
- The antibody may reduce immunogenic responses in clinical settings and has potential applications in APRIL-mediated diseases like Sjogren syndrome, multiple sclerosis, and systemic lupus erythematosus.
