Researchers Develop Promising Treatment for Colorectal Cancer Using Novel Radioimmunotherapy

Researchers from Memorial Sloan-Kettering Cancer Center have made a groundbreaking discovery in the fight against colorectal cancer. A new study has outlined the efficacy and safety of a novel radioimmunotherapy approach, providing new hope for patients suffering from this devastating disease. The research team has successfully developed a three-step pretargeted radioimmunotherapy (PRIT) regimen that targets cancer cells with unprecedented precision. By combining systemic antibody-based targeting with ionizing radiation, this treatment has shown significant promise in treating liver metastases in patients with colorectal cancer.

Key Takeaways:

• The researchers have developed a novel three-step PRIT regimen that utilizes a bispecific antibody targeting the cell surface glycoprotein A33, a tumor antigen target expressed on over 95% of primary and metastatic colorectal cancer.
• The regimen involves a clearing agent and a monovalent Lu-177 radiohapten called [Lu-177]Lu-ABD, which was recently replaced by a bivalent Lu-177 radiohapten called [Lu-177]Lu-Gemini to enhance tumor uptake and retention.
• The bivalent [Lu-177]Lu-Gemini demonstrated superior targeting and tumor activity retention compared to the monovalent [Lu-177]Lu-ABD, with more favorable blood and kidney therapeutic indices.
• The research team established two orthotopic CRC liver metastasis models and demonstrated the efficacy of the bivalent [Lu-177]Lu-Gemini in treating advanced CRC liver metastasis, with significant increases in median survival compared to controls.
• The treatments were well-tolerated and did not cause significant weight loss or hematologic changes, with no radiation-induced injuries identified in the kidneys or bone marrow of treated mice.
• The researchers concluded that three-step GPA33 DOTA-PRIT with Lu-177-Gemini has the potential to greatly reduce the administered activity while maintaining the efficiency of the PRIT platform in clinically relevant models of target-rich and target-poor metastatic CRC.

Statistics:

• The bivalent [Lu-177]Lu-Gemini showed superior tumor targeting efficacy and dosimetry compared to the monovalent [Lu-177]Lu-ABD, with a mean absorbed dose of 119.88 cGy/MBq and a higher therapeutic index for blood and kidney.
• In the DOTA-PRIT experiment, both monovalent and bivalent radiohapten regimens increased the median survival of treated mice compared to controls, with no statistical difference between treatment groups.
• The median survival times for mice treated with [Lu-177]Lu-ABD, [Lu-177]Lu-Gemini, and controls were 71 days, 81 days, and 18 days, respectively.
• The researchers noted that the treatments were well-tolerated, with no significant weight loss or hematologic changes observed in treated mice.

Sources:

• NewsRx. Researchers from Memorial Sloan-Kettering Cancer Center Report Findings in Xenografts (Gpa33-pretargeted Radioimmunotherapy With Mono-and Bivalent Dota-based Lu-177-labeled Radiohaptens In a Mouse Orthotopic Liver Xenograft Model of Metastatic ...). Immunotherapy Weekly. July 2, 2025; p 4326.