- Antibodies are immune system proteins that are capable of recognizing unique biomarkers called antigens.
- Newly discovered Antibody-Drug Conjugates (ADCs) may be a most promising next-generation antibody therapeutics for cancer.
A new drug delivery method was designed to treat cancers that may also include hard-to-treat solid and liquid tumors, finds a research study from The Scripps Research Institute (TSRI).
The research study led by the associate professor Christoph Rader, was published in the journal Cell Chemical Biology.
‘Antibody-Drug Conjugates can be a promising drug delivery method for cancer therapy.’
The newly designed method involves a class of drugs known as antibody-drug conjugates (ADCs), which may serve as the most promising next-generation antibody therapeutics for cancer.
Antibody-drug conjugates (ADCs) may deliver a cytotoxic payload in a way that is tumor-selective.
The United States Food and Drug Administration (FDA) has approved three Antibody-Drug Conjugates (ADCs), but these may neither attach the drug to a defined site on the antibody.
Rader, said, "We've been working on this technology for some time."
"It's based on the rarely used natural amino acid selenocysteine, which we insert into our antibodies. We refer to these engineered antibodies as selenomabs."
Antibodies are found to be large immune system proteins that are capable of recognizing the unique molecular markers on tumor cells called antigens.
Rader also noted that, antibodies are usually not potent enough to eradicate cancer. However, high specificity for antigens make them the ideal vehicles for drug delivery straight into the tumor cells.
"We now show for the first time that selenomab-drug conjugates, which are 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 author also noted that, the Antibody drug conjugates stability was found to be critical to its effectiveness. The research team also found that the new antibody drug conjugates were found to have excellent stability in human blood in vitro as well as in the circulating blood in animal models. The new antibody drug conjugates are highly effective against HER2 breast cancer which is difficult to treat, and also against CD138 multiple myeloma cells. These cells interestingly did not harm the healthy cells and tissues.
Xiuling Li, TSRI research associate, said, "The selenomab-drug conjugate significantly inhibited the growth of an aggressive breast cancer."
"Four of the five mice tested were tumor-free at the end of the experiment, a full six weeks after their last treatment."
Further investigations on similar ADCs will also be carried out. Rader, along with TSRI Professor Ben Shen, was awarded with $3.3 million from the National Cancer Institute of the National Institutes of Health inorder to test the highly cytotoxic natural products are discovered in the Shen lab using drug delivery vehicles as selenomabs.
- Xiuling Li, Christopher G. Nelson, Rajesh R. Nair, Lori Hazlehurst, Tina Moroni, Pablo Martinez-Acedo, Alex R. Nanna, David Hymel, Terrence R. Burke, Christoph Rader. Stable and Potent Selenomab-Drug Conjugates. Cell Chemical Biology, 2017; DOI: 10.1016/j.chembiol.2017.02.012