Related Experiment Video
Updated: Mar 1, 2026
Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
IL13RA2 targeted alpha particle therapy against glioblastomas
Anirudh Sattiraju1,2, Kiran Kumar Solingapuram Sai1,2, Ang Xuan3
1Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Abstract:
Glioblastoma (GBM) is the most aggressive primary malignant brain cancer that invariably results in a dismal prognosis. Chemotherapy and radiotherapy have not been completely effective as standard treatment options for patients due to recurrent disease. We and others have therefore developed molecular strategies to specifically target interleukin 13 receptor alpha 2 (IL13RA2), a GBM restricted receptor expressed abundantly on over 75% of GBM patients. In this work, we evaluated the potential of Pep-1L, a novel IL13RA2 targeted peptide, as a platform to deliver targeted lethal therapies to GBM. To demonstrate GBM-specificity, we radiolabeled Pep-1L with Copper-64 and performed in vitro cell binding studies, which demonstrated specific binding that was blocked by unlabeled Pep-1L. Furthermore, we demonstrated real-time GBM localization of [64Cu]Pep-1L to orthotopic GBMs using small animal PET imaging. Based on these targeting data, we performed an initial in vivo safety and therapeutic study using Pep-1L conjugated to Actinium-225, an alpha particle emitter that has been shown to potently and irreversibly kill targeted cells. We infused [225Ac]Pep-1L into orthotopic GBMs using convection-enhanced delivery and found no significant adverse events at injected doses. Furthermore, our initial data also demonstrated significantly greater overall, median and mean survival in treated mice when compared to those in control groups (p < 0.05). GBM tissue extracted from mice treated with [225Ac]Pep-1L showed double stranded DNA breaks, lower Ki67 expression and greater propidium iodide internalization, indicating anti-GBM therapeutic effects of [225Ac]Pep-1L. Based on our results, Pep-1L warrants further investigation as a potential targeted platform to deliver anti-cancer agents.
Insights
A novel peptide, Pep-1L, targets interleukin 13 receptor alpha 2 (IL13RA2) on glioblastoma (GBM). This targeted therapy shows promise in preclinical models, improving survival and demonstrating anti-cancer effects in mice with brain tumors.
Area of Science:
- Oncology
- Molecular Biology
- Radiochemistry
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with poor prognosis.
- Current treatments like chemotherapy and radiotherapy are often ineffective for recurrent GBM.
- Interleukin 13 receptor alpha 2 (IL13RA2) is highly expressed on GBM cells, making it a potential therapeutic target.
Purpose of the Study:
- To evaluate Pep-1L, a novel peptide targeting IL13RA2, as a platform for delivering lethal therapies to GBM.
- To assess the in vitro and in vivo targeting capabilities of Pep-1L.
- To investigate the safety and therapeutic efficacy of Pep-1L conjugated with Actinium-225 for GBM treatment.
Main Methods:
- Radiolabeling of Pep-1L with Copper-64 ([64Cu]Pep-1L) for in vitro cell binding and in vivo PET imaging.
- Convection-enhanced delivery of Pep-1L conjugated with Actinium-225 ([225Ac]Pep-1L) in orthotopic GBM mouse models.
- Assessment of therapeutic effects through survival studies, DNA damage analysis, Ki67 expression, and propidium iodide internalization.
Main Results:
- [64Cu]Pep-1L demonstrated specific binding to IL13RA2-expressing GBM cells in vitro and localized to orthotopic GBMs in vivo.
- [225Ac]Pep-1L treatment showed no significant adverse events and led to significantly improved survival in treated mice compared to controls.
- Evidence of anti-GBM effects, including DNA double-strand breaks, reduced proliferation (Ki67), and increased cell death (propidium iodide uptake), was observed in GBM tissues.
Conclusions:
- Pep-1L effectively targets IL13RA2-positive GBM cells.
- Pep-1L conjugated with [225Ac] shows promising safety and therapeutic potential against GBM in preclinical studies.
- Pep-1L warrants further investigation as a targeted delivery platform for anti-cancer agents in GBM treatment.
