Novel three-step pretargeted radioimmunotherapy offers safe, effective treatment
Researchers at Memorial Sloan Kettering Cancer Center in New York City and Massachusetts Institute of Technology in Boston have developed a new, three-step system that uses nuclear medicine to target and eliminate colorectal cancer. In this study with a mouse model, researchers achieved a 100-percent cure rate—without any treatment-related toxic effects. The study is reported in the November featured article in The Journal of Nuclear Medicine.
Until now, radioimmunotherapy (targeted therapy) of solid tumors using antibody-targeted radionuclides has had limited therapeutic success. “This research is novel because of the benchmarks reached by the treatment regimen, in terms of curative tumor doses, with non-toxic secondary radiation to the body’s normal tissues,” explains Steven M. Larson, MD, and Sarah Cheal, PhD, of Memorial Sloan Kettering Cancer Center. “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.”
Theranostics, a term derived from therapy and diagnostics, is the use of a single agent to both diagnose and treat disease. The theranostic agent first finds the cancer cells, then destroys them, leaving healthy cells unharmed—minimizing side effects and improving quality of life for patients.
In this study, the glycoprotein A33 (GPA33), an antigen found on over 95 percent of primary and metastatic human colorectal cancers, was targeted with a bispecific antibody for A33 tumor antigen and a second antibody for a small-molecule radioactive hapten, a complex of lutetium-177 (177Lu) and S-2-(4-aminobenzyl)1,4,7,10-tetraazacyclododecane tetra-acetic acid (177Lu-DOTA-Bn).
The DOTA-pretargeted radioimmunotherapy (PRIT) strategy was tested on a mouse model. In randomly selected mice undergoing treatment, serial SPECT/CT imaging was used to monitor treatment response and calculate radiation-absorbed doses to tumors. All the DOTA-PRIT–treated animals tolerated the treatment well, and all 9 assessed mice had no trace of cancer remaining upon microscopic examination. There was also no detectable radiation damage to critical organs, including bone marrow and kidneys.
The 100-percent cure rate in the mouse model is a promising preliminary finding that suggests that anti-GPA33-DOTA-PRIT will be a potent radioimmunotherapy regimen for GPA33-positive colorectal cancer tumors in humans.
According to the Centers for Disease Control and Prevention, colorectal cancer is the third most common cancer affecting both men and women. Each year, approximately 140,000 new cases are diagnosed in the United States and 50,000 people die of the disease.
The applications of this nuclear medicine treatment protocol could extend to other cancers as well. Larson and Cheal state, “If clinically successful, our approach will expand the repertoire of effective treatments for oncologic 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.” They add, “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.”
The Latest on: Colorectal cancer
- Cancer screening kit comes to N.W.T. region with high rate of colorectal canceron February 22, 2020 at 8:38 pm
Colorectal cancer is very treatable if caught early, but the screening rate for the disease in the Beaufort Delta region is well-below the national target rate.
- Study examines why colon cancer is more deadly in pediatric and young adult patientson February 21, 2020 at 8:11 am
Colon cancer is more likely to be lethal in children and young adults than middle-aged adults. In a single-institution study, researchers at The University of Texas MD Anderson Cancer Center, Houston, ...
- Early-onset colorectal cancer: initial clues and current viewson February 21, 2020 at 8:08 am
Over the past several decades, the incidence of early-onset colorectal cancer (EOCRC; in patients
- Three-dimensional culture models mimic colon cancer heterogeneity induced by different microenvironmentson February 21, 2020 at 2:08 am
Colorectal cancer demonstrates intra-tumour heterogeneity formed by a hierarchical structure comprised of cancer stem cells (CSCs) and their differentiated progenies. The mechanism by which CSCs are ...
- Israeli-made x-ray capsule identifies warning signs of colorectal canceron February 20, 2020 at 8:29 am
A swallowable capsule to x-ray and identify warning signs of colorectal cancer is edging closer to the American market, promising an Israeli-led revolution in colorectal cancer prevention. The small C ...
- Colorectal cancer partner-in-crime identifiedon February 20, 2020 at 7:28 am
A protein that helps colorectal cancer cells spread to other parts of the body could be an effective treatment target. Colorectal cancer is the second most common cancer in women and third most common ...
- Crohn's Boosts Risk of Death From Colorectal Canceron February 19, 2020 at 2:51 pm
Compared with the general population, individuals with Crohn's disease (CD) are at increased risk of developing and dying of colorectal cancer (CRC), according to the first population-based study of ...
- Medicaid expansion led to earlier breast, colon, lung cancer diagnosison February 19, 2020 at 9:45 am
In the latest study assessing the impact of the changes in eligibility allowed under Obamacare, those residing in states that opted to expand Medicaid were shown to be diagnosed with cancer earlier.
- Should Routine Colon Cancer Screeningon February 18, 2020 at 7:42 am
SAN FRANCISCO — For years, 50 years old has been the age at which screening for colorectal cancer (CRC) began in the United States, but recently one group lowered the starting age to 45. This move by ...
- GI Bleeding on Oral Anticoagulants in Atrial Fib Foremost a Colon Cancer Red Flagon February 14, 2020 at 12:59 pm
But those few with such bleeding showed a 10- to 15-fold increased 1-year risk for a diagnosis of colorectal cancer if they were older than 65, and 24 times that risk if they were 65 or younger, ...
via Google News and Bing News