Antibody-drug Conjugates Show Promise in Hard-to-Treat Cancers

Next-generation antibody treatments effectively deliver cytotoxic drugs to tumors.

The authors of a recent study published by Cell Chemical Biology created a novel drug delivery method that proved effective in animal models of hard-to-treat cancers.

The new approach includes antibody-drug conjugates (ADCs), which are a class of drugs that includes promising next-generation antibody treatments for cancer. ADCs are able to selectively deliver cytotoxic drugs to tumors and prevent widespread cellular harm. Thus far, the FDA has approved 3 ADCs, but none attach to a particular site on the antibody.

"We've been working on this technology for some time," said lead researcher Christoph Rader, PhD. "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 on their own are not usually able to fight cancer, despite their ability to recognize antigens. However, its cancer-detecting ability makes antibodies an excellent candidate as a vehicle for a targeted drug delivery approach, according to the study.

"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,” Dr Rader said.

The authors said that the stability of ADCs is crucial for the efficacy of the drug, along with its potency.

The investigators discovered that their new ADCs were highly stable in human blood in vitro and circulating blood in animal models. The authors also discovered that the new drugs were effective against HER2 breast cancer and CD138 multiple myeloma in these settings.

Notably, the novel ADCs were not observed to harm surrounding healthy cells and tissues, which is important to prevent side effects from cancer drugs in humans.

"The selenomab-drug conjugate significantly inhibited the growth of an aggressive breast cancer," said first study author Xiuling Li, PhD. "Four of the 5 mice tested were tumor-free at the end of the experiment, a full 6 weeks after their last treatment."

These findings are significant because traditional treatments can take much longer to be effective, and can carry severe adverse events. Additional studies are needed to determine whether the selenomab-drug conjugate can effectively treat these cancers in the human body.

The study authors plan to examine similar drugs in the future, and were the recipients of a $3.3 million grant from the National Cancer Institute of the National Institutes of Health. Through the grant, investigators plan to test highly cytotoxic natural products using selenomabs as drug delivery vehicles, the study concluded.