A novel radiopharmaceutical approach using a specially-designed mini-protein has shown promising results in delivering targeted radiation therapy to multiple cancer types. The findings, presented at a recent global cancer symposium in Barcelona, demonstrate how AKY-1189 can precisely target cancer cells while minimizing damage to surrounding healthy tissue.
AKY-1189 works by targeting Nectin-4, a protein abundantly expressed on the surface of various cancer cells but minimally present in normal tissues. This innovative approach represents a significant advancement in precision medicine for oncology.
Targeting Nectin-4: A Widespread Cancer Marker
Nectin-4 is expressed on cell membranes and commonly found in bladder, breast, lung, cervical, head and neck, and colorectal cancers. Its prevalence in up to 90% of patients with certain cancer types makes it an ideal target for therapeutic intervention.
Professor Mike Sathekge, Head of Nuclear Medicine at the University of Pretoria, explained the significance: "This is the first time we are seeing a completely new technology used 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 tumor."
AKY-1189 is designed to carry Actinium-225, a radioactive element with therapeutic potential. By binding specifically to Nectin-4, the mini-protein delivers a focused radiation dose to cancer cells while largely preserving healthy tissue.
Clinical Investigation in Advanced Cancer Patients
The research team obtained special regulatory permission to evaluate AKY-1189 in South Africa. Their study included 20 patients with metastatic cancers that had progressed despite standard treatments:
- 9 with metastatic bladder cancer
- 3 with metastatic breast cancer
- 3 with cervical cancer
- 2 with colorectal cancer
- 3 with non-small cell lung cancer
The investigation employed sophisticated imaging techniques to track the biodistribution of the radiopharmaceutical. Patients received [68Ga]Ga-AKY-1189 for PET-CT imaging at 1, 2, and 3 hours post-injection to visualize the protein's movement through the body and into tumors.
To assess radiation dosimetry, nine patients received [177Lu]Lu-AKY-1189, with SPECT-CT scans performed at 3, 24, and 48 hours after administration. This allowed researchers to quantify radiation absorption in various organs over time.
Encouraging Safety and Targeting Profile
Analysis of 15 patients revealed highly favorable results. The radiopharmaceutical demonstrated strong tumor targeting with rapid clearance from healthy tissues. Importantly, kidney uptake—often a concern with radiopharmaceuticals—was minimal, suggesting that a full six-dose treatment course with [225Ac]Ac-AKY-1189 could be safely administered.
The safety profile was particularly encouraging, with no significant adverse reactions observed in the skin or other organs. While the salivary glands showed transient uptake, this did not result in clinical toxicity. No evidence of renal or other organ damage was detected.
"We wanted to address the gap in care for patients whose cancer has grown beyond the part of the body it originated in or has spread to other parts of the body, and which had continued to progress on the local standard of care," Professor Sathekge noted.
Although these preliminary human studies were not designed as formal clinical trials to measure tumor response, they provided crucial data on the drug's ability to reach various cancer types with an acceptable safety profile.
Professor Sathekge emphasized: "The most important learning from our work here is that we can clearly see that the drug is taken up by different types of tumors and, as such, has great potential for treating those patients' tumors. Also, and this is very important, we saw that the drug does not accumulate in normal tissue and so could be safe for multiple administrations to maximize treatment impact."
Advancing to Formal Clinical Evaluation
Building on these promising results, a clinical trial is now being initiated for patients with advanced cancers at Professor Sathekge's institute. This study will evaluate AKY-1189's efficacy in tumor reduction and survival outcomes.
Aktis Oncology, the company developing AKY-1189, is also planning clinical studies in the United States to further validate the safety and effectiveness of this novel approach across diverse patient populations and healthcare settings.
Professor Timothy Yap, a cancer symposium co-chair not involved in the research, commented on the study's significance: "This interesting study shows that it is possible for a unique 'mini-protein,' AKY-1189, to target Nectin-4, a protein expressed in a number of different cancers. The imaging results presented today show how it is able to home in specifically on Nectin-4 with the radiation having 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."
Paradigm Shift in Cancer Treatment
AKY-1189 represents a potential paradigm shift in cancer therapy, aligning with the growing trend toward personalized and targeted treatments. Unlike conventional chemotherapy and radiation that often damage healthy cells, targeted radiopharmaceuticals like AKY-1189 aim to deliver therapeutic agents precisely to cancer cells.
This approach could be particularly valuable for patients with metastatic cancers that have become resistant to standard treatments. By delivering radiation directly to cancer cells across multiple tumor sites simultaneously, AKY-1189 offers a potential new option for these challenging cases.
While further research is necessary to fully establish efficacy, these early findings suggest that AKY-1189 could become an important addition to the oncologist's arsenal, potentially improving outcomes for patients with Nectin-4-expressing cancers.
