During the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, at Barcelona, Spain, a pioneering study introduced a novel "mini-protein" capable of delivering targeted radiation doses directly to cancer cells without affecting healthy tissues. Professor Mike Sathekge from the University of Pretoria and Steve Biko Academic Hospital in South Africa is leading this research, which is considered a breakthrough in targeted cancer therapy.

AKY-1189, a newly designed protein, specifically targets a protein known as Nectin-4. Nectin-4 is prevalent on the surface of cancer cells in various solid tumours, including bladder, breast, lung, cervical, and bowel cancers. Using AKY-1189, researchers have shown that it is possible to deliver a therapeutic radiation dose directly to tumours that express Nectin-4 while leaving healthy tissues unaffected.

Professor Sathekge stated, "We are witnessing the first use of a completely new technology for targeted radiation." “A small protein made to seek out a different protein that many cancers express, Nectin-4, was used to take radiation directly to the tumour.”

In the study, the researchers administered a single injection of AKY-1189 to 20 patients with advanced cancers that were unresponsive to standard treatments. The researchers scanned the patients using PET-CT imaging one, two, and three hours after injection to monitor the drug's distribution. We conducted additional dosimetry studies using SPECT-CT imaging up to 48 hours post-injection to understand the compound's dispersion in the body and its effects on organs, particularly the kidneys.

So far, the imaging results reveal promising data. The tumours absorbed significant amounts of radiation, while the radioactivity in healthy tissues diminished quickly. “AKY-1189 did not have any adverse effects, including on the skin. The salivary glands showed a transient uptake that did not amount to any clinically meaningful exposure to radiation,” noted Professor Sathekge. The researchers did observe a minor radiation uptake in the kidneys, but at levels that suggest patients could receive a full course of treatment safely.

Professor Timothy Yap, co-chair of the symposium from the University of Texas MD Anderson Cancer Centre, highlighted the potential of AKY-1189, stating, “This interesting study shows that it is possible for a unique'mini-protein’, AKY-1189, to target Nectin-4... with little or no effect in other, healthy cells. These are the first results for AKY-1189 in humans, and we look forward to hearing the results from the forthcoming clinical trials in due course.”

While this study was not a clinical trial to assess cancer response, it provides critical insights. “We were able to gather important information not just for the specific patients but also with respect to AKY-1189’s potential for future patients,” said Professor Sathekge. The data suggest that the mini-protein’s ability to target multiple tumour types could offer new hope for patients with metastatic cancers that have spread beyond their original sites.

The research team is now planning further clinical studies in metastatic bladder cancer and other tumours expressing Nectin-4, with a new study set to open soon at the Nuclear Medicine Research Infrastructure (NuMeRi) in Pretoria, South Africa. Additionally, the drug’s developer, Aktis, is preparing for trials in the United States.

This novel approach, if proven in larger clinical trials, could mark a significant step forward in cancer treatment, offering a targeted, safer option for patients with advanced, treatment-resistant cancers.