In a groundbreaking development, a new pre-targeted radioimmunotherapy (PRIT) system based on 225Ac-DOTA has demonstrated remarkable effectiveness in curing an aggressive form of intraperitoneal ovarian cancer in preclinical trials. This therapy, known as anti-HER2 225Ac-PRIT, targets the HER2 protein, commonly expressed in ovarian cancer. Published in the Journal of Nuclear Medicine, this research offers hope for treating a typically incurable disease with minimal side effects.
Epithelial ovarian cancer, the most lethal form of ovarian cancer, often presents as an advanced-stage disease, including peritoneal carcinomatosis, where cancer spreads throughout the peritoneal cavity. Patients diagnosed at an advanced stage face a grim prognosis, with a five-year overall survival rate ranging from 18 to 46 percent. The main causes of mortality in these cases are the extensive peritoneal disease burden and malignant bowel obstruction.
Dr. Sarah M. Cheal, from the Molecular Imaging Innovations Institute in the Department of Radiology at Weill Cornell Medical College in New York, emphasized the growing interest in alternative therapies, especially those targeting HER2, given the advancements in immune and targeted therapies over the past few decades. She stated, “In this study, we adapted our PRIT system to target HER2 in epithelial ovarian cancer and explored whether this could effectively treat the disease without significant toxicity.”
The preclinical study involved five groups of eight to ten nude mice, each bearing peritoneal carcinomatosis tumors. Two groups of mice received either one or two cycles of anti-HER2 225Ac-PRIT treatment, while the other groups received alternative treatments or none at all and served as controls. Researchers monitored weekly weights and tumor progression for up to 154 days.
In untreated mice, tumors spread rapidly, resulting in a median survival of approximately four months. However, mice treated with one or two cycles of anti-HER2 225Ac-PRIT did not reach a median survival limit within the 154-day observation period. Remarkably, at the end of the study, 75 percent of mice in the anti-HER2 225Ac-PRIT treatment groups were confirmed to be clinically cured. Importantly, all treatments were well-tolerated by the mice, highlighting the therapy’s safety profile.
Dr. Steven M. Larson, from the Department of Radiology at Memorial Sloan Kettering Cancer Center in New York, noted, “In this study, we achieved high potency with anti-HER2 225Ac-PRIT while maintaining an acceptable safety profile. These findings suggest that when scaled to human patients, we can achieve curative tumor radiation-absorbed doses without major normal organ toxicity.
Moreover, Dr. Nai-Kong V. Cheung, from the Department of Pediatrics at Memorial Sloan Kettering Cancer Center, pointed out the modularity of DOTA-based PRIT, explaining that it can be adapted to target other cancers. He also mentioned the potential for next-generation PRIT using SADA (Self-Assembling Disassembling Antibody), which could have broad applications for compartmental therapies, such as peritoneal, as well as systemic theragnostic in oncology.
This groundbreaking research represents a significant step forward in the treatment of advanced ovarian cancer. The ability of anti-HER2 225Ac-PRIT to cure the disease in preclinical models with minimal side effects offers hope for patients who currently face limited treatment options and a challenging prognosis.
The therapy’s success in targeting the HER2 protein, which is prevalent in ovarian cancer, demonstrates the potential of precision medicine in the fight against cancer. By specifically targeting cancer cells while sparing healthy tissues, PRIT has the potential to revolutionize cancer treatment and improve outcomes for patients with advanced ovarian cancer.
As further studies and clinical trials are conducted to validate these findings and explore the therapy’s applicability in human patients, the medical community remains optimistic about the possibility of a groundbreaking treatment option for this deadly disease. The modularity and adaptability of DOTA-based PRIT suggest that this innovative approach could be extended to other cancer types, opening new avenues for personalized cancer treatment.
