Gel-forming therapeutic peptide exhibits sustained delivery and efficacy in a mouse model of triple-negative breast cancer

Akash Patil; Adam C Mirando; Ioanna Liatsou; George Sgouros; Aleksander S Popel; Niranjan B Pandey

doi:10.1016/j.peptides.2023.171075

Gel-forming therapeutic peptide exhibits sustained delivery and efficacy in a mouse model of triple-negative breast cancer

Peptides. 2023 Nov:169:171075. doi: 10.1016/j.peptides.2023.171075. Epub 2023 Aug 15.

Authors

Akash Patil¹, Adam C Mirando², Ioanna Liatsou³, George Sgouros³, Aleksander S Popel⁴, Niranjan B Pandey⁵

Affiliations

¹ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: [email protected].
² Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; AsclepiX Therapeutics, Inc., Baltimore, MD, USA. Electronic address: [email protected].
³ Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; AsclepiX Therapeutics, Inc., Baltimore, MD, USA.

Abstract

Triple-negative breast cancer (TNBC) is a particularly aggressive and invasive subtype of breast cancer that represents a major cause of death of women worldwide. Here we describe the efficacy of an integrin-binding antiangiogenic peptide in a variety of delivery methods and dosing conditions. This peptide, AXT201, demonstrated consistent anti-tumor efficacy when administered intraperitoneally, subcutaneously, and intratumorally, and retained this activity even when dosing frequency was reduced to once every two weeks. Finally, in vivo imaging and biodistribution studies of AXT201 showed a long-term persistence of at least 10 days at the site of injection and a stable detectable signal in the blood over 48 h, indicating a sustained release profile. Taken together, these findings indicate AXT201 exhibits favorable pharmacokinetic properties for a 20-mer peptide.

Keywords: Angiogenesis; Biodistribution; Drug delivery; Pharmacokinetics; Therapeutic peptide; Triple-negative breast cancer.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Cell Line, Tumor
Female
Humans
Mice
Peptides / therapeutic use
Tissue Distribution
Triple Negative Breast Neoplasms* / drug therapy
Triple Negative Breast Neoplasms* / pathology

Substances

Peptides

Grants and funding

R01 CA138264/CA/NCI NIH HHS/United States