#5 Antibody Drug Conjugates

Overview

Scientists have learned more about cancer in the last two decades than had been learned in all the centuries preceding. And even though one million people in the United States develop cancer annually, tremendous advances have been made in cancer biology that have led to significant progress not only in cancer prevention and early detection but in cancer treatment as well.

While chemotherapy with its many drugs that damage and destroy cancer cells—but also harm surrounding healthy cells—is still the only form of treatment available for some cancers, we now have a new class of potent drugs called antibody-drug conjugates that are designed to treat certain advanced cancers that have spread to other parts of the body.

The century-old dream of creating magic bullets to fight cancer is almost here. Antibody-drug conjugates represent a promising therapeutic approach for advanced cancer patients by combining the antigen-targeting specificity of monoclonal antibodies with the cytotoxic potency of chemotherapeutic medications that specifically target a protein only found in or around tumor cells, and then using this drug combination to destroy tumors. Think precision killing with fewer side effects.

For a drug delivery system, drug conjugates use antibodies, the large molecules in the immune system that typically bind to the cell surface of a virus or bacteria and keep it from advancing. The antibodies used for conjugates are now created in a laboratory and are specifically engineered so that a patient’s immune system won’t consider them foreign and set out to destroy them.

The new antibodies are then joined to several molecules of a highly potent toxin that targets a protein that is only found in or around cancer cells, and special linkers are used to hold them together. It’s this unique combination of antibody, toxin, and linker are that forms the drug conjugate, which is then used to target the rogue microscopic targets throughout a patient’s body.

Once intravenously given to a patient, it’s the linker that keeps the antibody and toxin latched together over the course of weeks as the drug works its way through the bloodstream in search of specific cancer cells.

Since the drug conjugate has been designed to attach only to a specific protein found in high numbers on the targeted cancer, the compound intentionally ignores all healthy cells, as they lack the particular protein that has been scheduled for destruction.

The antibody acts like a homing signal, and once the cancer cell has been located, the drug conjugate binds to it and is eventually pulled inside by the cancer cell, because it considers the antibody an ally. Study results have shown that this Trojan Horse strategy works and once entry is made, the powerful toxin is released, damaging the cancer cell as it tries to divide, resulting in eventual cancer cell death.

With over two dozen antibody-drug conjugates currently in clinical trials for solid tumors and blood cancer, as well as potent FDA-approved drugs for advanced HER2-positive breast cancer and Hodgkin’s lymphoma already available, it is becoming clear that these smart bombs, the antibody-drug conjugates, are becoming an important and viable approach for selectively delivering highly cytotoxic agents to tumor cells while avoiding damage to normal tissue.

 

Where Are They Now

Currently there are over 350 antibody drug conjugates (ADCs) being developed to fight cancer, with previously approved drugs in trials to prove efficacy against a larger variety of cancers. Many pharmaceutical and research companies are investing millions of dollars into the growing ADC market, which is projected to reach $3 billion by 2018. Approval was recently granted to two ADCs and more are expected to gain approval with emerging data from numerous ongoing clinical trials. Recently, the first wave of site-specific ADCs were promoted to clinical trials. Positive results from one of the first clinical trials of an antibody drug conjugate were released in 2017.

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