Roughly a century ago, German immunologist Paul Ehrlich was staining cell cultures when he had a radical thought. He wondered, if staining techniques could target a single strain of bacteria, then what’s to stop scientists from eventually developing a “magic bullet” treatment for every disease, one that is highly targeted and has few or no side effects? As a chemotherapy pioneer, Ehrlich even broadened this notion to include cancers.
Though he never saw anything like it in his lifetime, today, Ehrlich’s dream may have been finally realized. That’s because scientists are currently testing an experimental form of cancer treatment, called antibody-drug conjugates (ADCs).
This unusual form of cancer treatment combines homing ability of human antibodies with the cancer-killing power of chemo drugs or cytotoxins. Such innovations may soon be the “magic bullet” for treating malignant pleural mesothelioma (MPM) and other severe diseases.
A new direction in mesothelioma research
ADCs have gotten quite a bit of attention lately, and for good reason. Clinical studies have shown that a such drugs can have remarkable tumor-shrinking properties, while causing fewer and less severe side effects than traditional chemotherapies.
In fact, ADCs are such a hot topic right now that they recently appeared as the subject of a New York Times article on cutting-edge breast cancer therapies.
Stephen Evans-Freke, a general partner of a pharma investment firm, told the newspaper that preliminary ADC trial results make them look exceedingly promising – for patients and pharmaceutical manufacturers alike.
“I don’t think there is a major pharma or a mid-sized pharma with interest in cancer that doesn’t have [an ADC] program or isn’t scrambling to put one together,” he explained.
So what are ADCs and how do they work?
Two halves, linked
At its simplest, an ADC consists of three things. First, a human antibody (or immune protein) that identifies a specific form of cancer. This is then attached to a chemotherapy agent or cytotoxin. The third bit, and a critical one at that, is the small molecule that links the first two.
When introduced into the bloodstream, ADCs do not attack indiscriminately, they way traditional chemo agents do. Instead, their targeted antibodies allow them to seek out tumors and deliver the cytotoxins, which then kill malignant cells.
According to the Society of Toxicology, this unique construction makes ADCs something of a molecular guided missile, increasing the maximum tolerated dose and decreasing the minimum effective dose.
And their targeted nature gives ADCs unmatched potential. In an article for Genetic Engineering and Biotechnology News (GEBN), pharma developer ImmunoGen estimated that ADCs are often between 1,000 and 10,000 as potent as typical chemo drugs.
All these characteristics could make these novel formulations a welcome new weapon in the fight against mesothelioma.
A not-so-novel idea, reborn
While ADCs may sound brand-new, they have been in the works since the 1980s. However, according to GEBN, they suffered a decline in popularity that lasted nearly 25 years. It only ended around 2005, when clinical trials began revealing the wonders that such drugs can accomplish.
Today, dozens of ADCs are in development, at least one for every major type of cancer – MPM included. In 2011, researchers from Bayer Pharmaceuticals registered BAY 94-9343, an ADC that targets mesothelin, a protein that is overproduced in all forms of mesothelioma.
Using a cytotoxin called DM4, this drug binds to and kills only cells that produce mesothelin – and the more mesothelin a malignant cell creates, the more likely it is to absorb BAY 94-9343 and die.
At Kazan, McClain, Lyons, Greenwood and Harley, we know that it’s treatment developments like this that give MPM patients continued hope of living a longer, fuller life.