Novel radiolabeled antibody developed for diagnosis and treatment of solid tumors

A newly developed radiolabeled antibody that targets the cancer antigen IL13Rα2 has been found to be highly specific, binding only to cancer cells and not to the related antigen IL13Rα1, which is widely expressed in healthy tissues. Tested in multiple cancer types, the radiolabeled antibody was effective at delineating malignancies at a low injected mass dose and has the potential to be translated into radioimmunotherapy applications.

This research was published in the April issue of The Journal of Nuclear Medicine.

Interleukin-13 receptor α-2 (IL13Rα2) is a cell surface receptor frequently expressed in solid malignancies, such as glioblastoma, melanoma, and breast cancer. IL13Rα2 has limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor detection.

“So far, no IL13Rα2-targeting antibodies for diagnostic and therapeutic (theranostic) applications exist in the clinic,” said Simone Krebs, MD, associate professor at the University of Texas MD Anderson Cancer Center in Houston, Texas.

“My colleagues and I sought to develop a radiolabeled antibody that would achieve high and prolonged tumor uptake and retention, facilitating delivery of cytotoxic radiation predominantly to tumors while sparing normal tissues.” The antibody development project was undertaken during her tenure at Memorial Sloan Kettering Cancer Center.

In the study, five novel human anti-IL13Rα2 antibodies (KLG-1–5) were developed. In vitro binding properties and target specificity were assessed, and in vivo ⁸⁹Zr-immuno-PET was conducted in a glioblastoma mouse model. Upon selection of KLG-3 as the leading candidate, a mass dose titration study was conducted.

Next, ex vivo biodistribution results were used to determine effective dosimetry of ¹⁷⁷Lu-labeled KLG-3 therapy. Targeting with KLG-3 was also evaluated in a melanoma mouse model.

Lead candidate anti-IL13Rα2 antibody KLG-3 validated highly specific target binding in human glioblastoma and melanoma models, resulting in high-contrast PET images with minimal accumulation in off-target healthy tissues. Prospective dosimetry of its ¹⁷⁷Lu-labeled counterpart suggested therapeutic efficacy at relatively low injected activities, supporting further pursuit of KLG-3 as a potential radioimmunotherapy.

“These results demonstrate a significant advance in the use of IL13Rα2 as a viable target in cancer therapy,” stated Krebs. “Implementation of the targeting moieties developed in this study may lead to highly specific and efficacious tumor-targeted drugs with little side effects to the patients.

She continued, “IL13Rα2 is known to be a harbinger of immunosuppression, and thus, IL13Rα2-targeted Immuno-PET may identify this molecular phenotype, which could aid in patient selection and an understanding of who may benefit from combinatorial strategies.”

Provided by
Society of Nuclear Medicine and Molecular Imaging