Radioimmunotherapy System Effectively Treats Colorectal Cancer

A new study describes a three-step theranostic nuclear medicine strategy that targets and eliminates colorectal cancer without any treatment-related toxic effects.

Developed at the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA) and Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY, USA), the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid pretargeted radioimmunotherapy (DOTA-PRIT) strategy is based on a glycoprotein bispecific antibody and a small-molecule radioactive hapten. In the murine study, the researchers used a fractionated 3-cycle regimen that targeted glycoprotein A33 (GPA33), an antigen found on over 95% of primary and metastatic human colorectal cancers.

In the mice undergoing treatment, serial single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was used to monitor treatment response and calculate radiation-absorbed doses to tumors. The results revealed a 100% cure rate, with all DOTA-PRIT-treated animals tolerated the treatment well. All mice had no trace of cancer remaining upon microscopic examination, and there was no detectable radiation damage to critical organs, including bone marrow and kidneys. The study was published in the November 2017 issue of The Journal of Nuclear Medicine.

“Until now, radioimmunotherapy of solid tumors using antibody-targeted radionuclides has had limited therapeutic success,” concluded lead author Sarah Cheal, PhD, of MSKCC, and colleagues. “The success in murine tumor models comes from the unique quality of the reagents developed by our group, and the reduction to practice methodology, including a theranostic approach that can be readily transferred, we believe, to patients.”

“The system is designed as a 'plug and play' system, which allows for the use of many fine antibodies targeting human tumor antigens and is applicable, in principle, to virtually all solid and liquid tumors in man. If clinically successful, our approach will expand the repertoire of effective treatments for oncologic patients,” said senior author Steven Larson, MD, of MSKCC. “There is a huge unmet need in oncology, especially for the solid tumors, for curative treatments for advanced disease. This includes, colon, breast, pancreas, melanoma, lung, and esophageal, to name a few.”

Theranostics uses specific biological pathways to acquire diagnostic images and deliver a therapeutic dose of radiation. Once a specific diagnostic test shows a particular molecular target on a tumor, the therapy agent can be specifically targeted to that receptor, providing a more targeted and efficient form of pharmacotherapy.

Related Links:
Massachusetts Institute of Technology
Memorial Sloan-Kettering Cancer Center