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SNMMI 2016: Pretargeted Radioimmunotherapy Eliminates Colorectal Cancer in Preclinical Studies

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Key Points

  • An investigative treatment called pretargeted radioimmunotherapy harnesses an antibody that attaches to the cell-surface antigen glycoprotein A33, which is hyperexpressed in many colon cancers.
  • Researchers united the anti-GPA33 antibody with radionuclide agents that deliver a powerful dose of radiation directly to the tumor.

Presenters at the 2016 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) unveiled a novel radioimmunotherapy that combines a cancer-seeking antibody with potent radionuclide agents, resulting in complete remission of colorectal cancer in mouse models (Scientific Paper 33).

Theranostic drugs—a type of diagnostic therapy for individual patients that tests them for possible reaction to taking new medication and then tailors a treatment plan based on the test results—are powerful newcomers in oncology’s arsenal. In addition to providing targeted treatment, in many cases they double as imaging agents that can monitor the effectiveness of therapy.

Study Findings

An investigative treatment called pretargeted radioimmunotherapy harnesses an antibody that attaches to the cell-surface antigen glycoprotein A33, which is hyperexpressed in the vast majority of colon cancers, whether primary or metastatic. Researchers united the anti-GPA33 antibody with radionuclide agents that deliver a powerful dose of radiation directly to the tumor. The technique was found to be entirely curative in this preliminary mouse study.

“If these results can be replicated in prospective human studies, this multiplatform approach could be used with an array of antibodies to treat a number of cancers, especially colorectal and ovarian cancers,” said presenting author Sarah M. Cheal, PhD, Senior Research Scientist at Memorial Sloan Kettering Cancer Center.

For this study, researchers tested the efficacy of anti-GPA33 with radiotherapies using lutetium-177 benzylDOTA (Lu-177 DOTA-Bn) in mice bearing colorectal cancer grafts. In the same group of animals, the researchers were able to detect solid tumors of 10 mg or less during the course of a fractionated treatment regimen that achieved complete cures in all solid tumors without any collateral toxicity. This platform of theranostic radioimmunotherapy could have broad applicability.

To see an illustration of three-step DOTA-PRIT based on targeting with an IgG-scFv bispecific antibody (eg, huA33-C825 for detection and treatment of colorectal cancer) with dual specificity for a tumor-associated antigen (eg, GPA33) and M-DOTA haptens (eg, Lu-177 DOTA), click here. Credit: © Memorial Sloan Kettering Cancer Center 2016.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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