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Published on: August 23, 2019
Highly specific antiangiogenic therapy is effective in suppressing growth of experimental Wilms tumors
1Division of Pediatric Surgery, Department of Pathology, College of Physicians & Surgeons, Columbia University, and Babies & Children's Hospital of New York, the New York Presbyterian Hospital, New York, NY, USA.
Background/Purpose:
Pathologic angiogenesis in tumors is a potential target for novel therapies. Vascular endothelial growth factor (VEGF) is an angiogenic promoter present in a wide variety of human tumors. VEGF is expressed as 4 isoforms; one of these, VEGF165, predominates in human tumors. The authors hypothesized that antagonism of VEGF165 by a specific aptamer would block tumor growth in an experimental model of Wilms tumor.
Methods:
VEGF isoform expression in clinical (n = 2) and experimental tumors were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Tumors were induced in NCR nude mice (n = 32) by intrarenal injection of 10(6) cultured Wilms tumor cells. At 1 week, aptamer (n = 16) or vehicle (n = 16) treatment was started and continued daily for 5 weeks.
Results:
At 6 weeks tumors weighed 84% less in treated versus control animals (0.69 v 4.41 g; P <.028), without observed adverse effects and similar to suppression previously reported using nonisoform-specific anti-VEGF antibody (94% to 96%).
Conclusions:
Anti-VEGF165 aptamer effectively suppressed primary tumor growth in experimental animals with no observed adverse effects. Development of highly specific antiangiogenic therapies may be of particular benefit to pediatric patients.
Insights
A novel anti-angiogenic aptamer targeting Vascular Endothelial Growth Factor 165 (VEGF165) significantly reduced Wilms tumor growth in mice by 84% without adverse effects, showing promise for targeted cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Pathologic angiogenesis, driven by vascular endothelial growth factor (VEGF), is a key target for anti-cancer therapies.
- VEGF165 is the predominant isoform in human tumors.
- Specific antagonism of VEGF165 may offer a targeted therapeutic approach.
Purpose of the Study:
- To investigate the efficacy of a VEGF165-specific aptamer in inhibiting tumor growth.
- To evaluate the safety profile of this targeted anti-angiogenic therapy.
Main Methods:
- VEGF isoform expression was assessed via RT-PCR in clinical and experimental tumors.
- Wilms tumor xenografts were established in nude mice.
- Mice received daily aptamer or vehicle treatment for 5 weeks.
Main Results:
- Aptamer treatment resulted in an 84% reduction in tumor weight compared to controls (0.69g vs 4.41g, P < .028).
- No adverse effects were observed in the aptamer-treated group.
- Tumor suppression was comparable to previously reported non-isoform-specific anti-VEGF antibodies.
Conclusions:
- A VEGF165-specific aptamer effectively suppressed primary tumor growth in an experimental Wilms tumor model.
- The aptamer demonstrated a favorable safety profile.
- Highly specific anti-angiogenic therapies, like this aptamer, hold potential for pediatric cancer treatment.
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