Radionuclide therapy a promising option to treat HER2 breast cancer

The radionuclide treatment combines radioactive iodine therapy with single-domain antibodies to target the HER2 antigen.

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A Phase I trial has found that radionuclide treatment may offer new therapeutic options for human epidermal growth factor receptor type 2 (HER2)-positive breast cancer. The treatment combines radioactive iodine therapy with single-domain antibodies that target the HER2 antigen to destroy cancer cells. 

Currently, there are no HER2-targeting radiopharmaceuticals available to patients. However, with the development of the new targeted radionuclide theranostic agent, 131I-GMIB-Anti-HER2-VHH1, researchers sought to evaluate its safety, biodistribution, radiation dosimetry and tumour-imaging potential with the goal to introduce a new mechanism of action in the treatment of HER2-positive breast cancer.

The study, published in The Journal of Nuclear Medicine, involved six healthy volunteers and three HER2-positive breast cancer patients received injections of 131I-GMIB-Anti-HER2-VHH1. Vital signs and bloodwork, as well as open-ended questions, were used to assess the safety of the radionuclide. Whole-body imaging was conducted to ascertain biodistribution information and the resulting image data determined the dosimetry. In the three subjects with breast cancer, imaging was also used to measure tumour uptake.

131I-GMIB-anti-HER2-VHH1 was found to be safe and stable after administration and to clear rapidly from the blood in healthy volunteers and the tracer accumulated in metastatic sites of patients with HER2-positive breast cancer.

“This research is the first step in the clinical development of 131I-GMIB-Anti-HER2-VHH1 for the treatment of this devastating cancer indication,” commented Marleen Keyaerts, principal investigator of the study. “As a result of this study, multi-centre dose escalation and therapeutic clinical investigation of 131I-GMIB-anti-HER2-VHH1 in patients with HER2-positive breast and gastric cancer is underway.”

According to the team, single-domain antibodies, such as 131I-GMIB-Anti-HER2-VHH1, could prove to be very beneficial in the future. “Single-domain antibodies are attractive probes for targeted radionuclide therapy and imaging due to their high binding specificity, sub-nanomolar affinity and low immunogenicity,” explained study sponsor Tony Lahoutte. “The findings outlined in this publication demonstrate the potential of iodinated single domain antibodies to serve as imaging agent and therapy for cancer patients.”