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We developed a chimeric fusion of human VEGF-A<jats:sub>121<\/jats:sub> with the carrier protein Elastin-like Polypeptide (ELP-VEGF) to induce therapeutic angiogenesis via targeted renal VEGF therapy. We previously showed that ELP-VEGF improves renal vascular density, renal fibrosis, and renal function in swine models of chronic renal diseases. However, VEGF is a potent cytokine that induces angiogenesis and increases vascular permeability, which could cause undesired off-target effects or be deleterious in a patient with a solid tumor. Therefore, the current study aims to define the toxicological profile of ELP-VEGF and assess its risk for exacerbating tumor progression and vascularity using rodent models. A dose escalating toxicology assessment of ELP-VEGF was performed by administering a bolus intravenous injection at doses ranging from 0.1 to 200\u00a0mg\/kg in Sprague Dawley (SD) rats. Blood pressure, body weight, and glomerular filtration rate (GFR) were quantified longitudinally, and terminal blood sampling and renal vascular density measurements were made 14\u00a0days after treatment. Additionally, the effects of a single administration of ELP-VEGF (0.1\u201310\u00a0mg\/kg) on tumor growth rate, mass, and vascular density were examined in a mouse model of breast cancer. At doses up to 200\u00a0mg\/kg, ELP-VEGF had no effect on body weight, caused no changes in plasma or urinary markers of renal injury, and did not induce renal fibrosis or other histopathological findings in SD rats. At the highest doses (100\u2013200\u00a0mg\/kg), ELP-VEGF caused an acute, transient hypotension (30\u00a0min), increased GFR, and reduced renal microvascular density 14\u00a0days after injection. In a mouse tumor model, ELP-VEGF did not affect tumor growth rate or tumor mass, but analysis of tumor vascular density by micro-computed tomography (\u03bcCT) revealed significant, dose dependent increases in tumor vascularity after ELP-VEGF administration. ELP-VEGF did not induce toxicity in the therapeutic dosing range, and doses one hundred times higher than the expected maximum therapeutic dose were needed to observe any adverse signs in rats. In breast tumor\u2014bearing mice, ELP-VEGF therapy induced a dose-dependent increase in tumor vascularity, demanding caution for potential use in a patient suffering from kidney disease but with known or suspected malignancy.<\/jats:p>","DOI":"10.1038\/s41598-021-85693-6","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T16:48:15Z","timestamp":1616086095000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A dose-escalating toxicology study of the candidate biologic ELP-VEGF"],"prefix":"10.1038","volume":"11","author":[{"given":"Jamarius P.","family":"Waller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Engel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro R.","family":"Chade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Gene L.","family":"Bidwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"85693_CR1","doi-asserted-by":"publisher","first-page":"A7","DOI":"10.1053\/j.ajkd.2018.01.002","volume":"71","author":"R Saran","year":"2018","unstructured":"Saran, R. et al. 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