The Scripps Research Institute (TSRI) from the Florida campus have developed a new drug delivery method that produces strong results in treating cancers in animal models that includes some hard-to-treat solid and liquid tumors. TSRI Associate Professor Christoph Rader led the study, and the article was published online in the journal Cell Chemical Biology.
A class of pharmaceuticals known as antibody-drug conjugates (ADCs) includes some of the most promising next-generation antibody therapeutics for cancer. A cytotoxic payload can be delivered in a way that is tumor-selective and 3 of the ADCs have been approved by the U.S. Food and Drug Administration (FDA), but are not attached to a defined site on the antibody as yet. They have been working on this technology for some time and it is based on the rarely used natural amino acid selenocysteine that we insert into our antibodies. The engineered antibodies are referred to as selenomabs.
Antibodies are large immune system proteins that recognize unique molecular markers on tumor cells called antigens. Antibodies, on their own, are usually not potent enough to eradicate cancer, but their high specificity for antigens makes them ideal for drug delivery straight to tumor cells.
For the first time it has been shown that selenomab-drug conjugates (ADCs that utilize the unique reactivity of selenocysteine for drug attachment) are highly precise, stable and potent compositions and promise broad utility for cancer therapy. The ADC’s stability is critical to its effectiveness and researchers found that their new ADCs showed excellent stability in human blood in vitro and in circulating blood in animal models. Also, the new ADCs were highly effective against HER2 breast cancer and against multiple myeloma. The ADCs did not harm healthy cells and tissues.
The drug significantly inhibited the growth of an aggressive breast cancer and four of the five mice tested were tumor-free at the end of the experiment which was a full six weeks after their last treatment.
They plan to investigate similar ADCs in the future. Rader and TSRI Professor Ben Shen were awarded $3.3 million from the National Cancer Institute of the National Institutes of Health to test highly cytotoxic natural products discovered in the Shen lab using selenomabs as drug delivery vehicles.
Both Rader and Li are authors of the study, “Stable and Potent Selenomab-Drug Conjugates” along with several others of the National Cancer Institute and the H. Lee Moffitt Cancer Center. The National Institutes of Health, the Intramural Research Program of the National Cancer Institute, the Lymphoma Research Foundation, the Klorfine Foundation and the Holm Charitable Trust, supported the study.
Dr Fredda Branyon