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Updated: Jun 23, 2026
Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
Antitumor activity of endogenous mFlt4 displayed on a T4 phage nanoparticle surface
Shun-xiang Ren1, Zhao-jun Ren, Min-yi Zhao
1Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Aim:
Flt4 plays a key role in promoting tumor metastasis by stimulating solid tumor lymphangiogenesis. In this study, mouse Flt4 (mFlt4) was displayed on T4 phage in order to explore the feasibility of breaking immune tolerance to "self-antigens" and to evaluate the phage's antitumor activity.
Methods:
A T4 phage nanometer particle expressing mFlt4 on the surface was constructed for evaluation as a recombinant vaccine. The presence of the mFlt4 gene in the T4-mFlt4 recombinant vaccine was verified by PCR and Western blot analysis. The immunotherapeutic potential of T4-mFlt4 was tested in mice injected with Lewis lung carcinoma (LLC) cells. Anti-Flt4 antibody producing B cells were detected by ELISPOT. The effects of T4-mFlt4 on lymphatic metastasis and lymphangiogenesis were investigated in a mouse antimetastasis assay and by Flt4 and CD105 immunohistochemistry.
Results:
The T4-mFlt4 recombinant vaccine demonstrated antitumor activity and elicited autoantibodies against mFlt4. Mice carrying LLC-derived tumors exhibited prolonged survival when given the vaccine compared with control-treated animals. The vaccine also inhibited lymphangiogenesis and tumor metastasis in the mouse models. However, T4-mFlt4 was not observed to inhibit tumor growth.
Conclusion:
The T4-mFlt4 recombinant vaccine induced protective antitumor immunity and antimetastasis against LLC. Induction of an autoimmune response directed against tumor progression merits further study as a new strategy for immunotherapy in cancer.
Insights
This study developed a T4 phage vaccine displaying mouse Flt4 (mFlt4) to combat tumor metastasis. The vaccine showed antitumor and antimetastasis effects in mice, highlighting a novel immunotherapy strategy.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Flt4 promotes tumor metastasis by stimulating lymphangiogenesis.
- Breaking immune tolerance to self-antigens is a potential cancer therapy approach.
Purpose of the Study:
- To display mouse Flt4 (mFlt4) on T4 phage as a recombinant vaccine.
- To evaluate the vaccine's ability to break immune tolerance and its antitumor activity.
Main Methods:
- Constructed a T4 phage nanometer particle expressing mFlt4.
- Verified mFlt4 presence using PCR and Western blot.
- Assessed immunotherapeutic potential in Lewis lung carcinoma (LLC) mouse models, detecting anti-Flt4 B cells via ELISPOT.
- Investigated effects on lymphangiogenesis and metastasis using antimetastasis assays and immunohistochemistry.
Main Results:
- The T4-mFlt4 vaccine demonstrated antitumor activity and induced autoantibodies against mFlt4.
- Mice treated with the vaccine showed prolonged survival and inhibited lymphangiogenesis and metastasis.
- The vaccine did not inhibit primary tumor growth.
Conclusions:
- The T4-mFlt4 recombinant vaccine induced protective antitumor immunity and antimetastasis effects against LLC.
- Inducing an autoimmune response against tumor progression is a promising immunotherapy strategy.
