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Recently, Eureka featured an article written by Chuck Harrison who has over 30 years of cancer drug discovery and development experience in preclinical and translational settings. The article Magic Bullets: The Next Evolution in Targeted Cancer Therapy  The article discussed how new ‘armed antibodies’ represent proverbial magic bullets–envisioned by a Nobel Laureate 100 years ago can kill tumors with greater efficacy and fewer side effects.

Excerpt from the article:

In the early 1900s, German Nobel Laureate Paul Ehrlich imagined an ideal therapy for disease, a drug precisely targeted to an invader, which if linked to a toxic chemical would act like a missile, carrying a destructive payload directly to the disease. Ehrlich said the drug would be a ‘Magische Kugel,’ which in English means ‘Magic Bullet.’ Such a therapy, he theorized, would be ideal for countless diseases, including cancer. Science had the payload. What it didn’t have was the missile.

Whether the idea came in a dream, whether it arrived as a classical “aha” moment in a dusty lab, or at a patient’s bedside while scribbling notes, the search for Ehrlich’s Magic Bullet took a huge leap when someone asked, “Why not antibodies?”

Antibodies are proteins made by the immune system. In the body, they bind with high specificity to antigens, receptors on the surface of foreign invaders, such as viruses and bacteria. Fitting like a lock in a key, such binding enables immune cells to “see” and attack invaders. And because Nature has innumerable invaders, the human body has many antibodies–10 million to be exact.

Scientists had their missile.

In 1975, Georges Kohler and Cesar Milstein created the first laboratory-produced antibodies, called monoclonal antibodies (mAbs). A year later, on Thanksgiving Day, a doctor named Ron Levy ran a groundbreaking experiment, inspiring him to run through the halls of his lab with joy. He’d created monoclonal antibodies that specifically recognized cancer cells.

In 1979, immunologist and cancer researcher Lee Nadler teamed up with Phil Stashenko, another immunologist, and created a monoclonal antibody targeted to antigens on non-Hodgkin’s lymphoma cells. Their drug failed. When given to a man with advanced lymphoma, the mAb bound to few tumor cells. And the patient’s immune system rejected the drug, due to the fact it was created from mouse cells.

To avoid rejection, scientists from IDEC Pharmaceuticals Corporation used recombinant technology to create a part human, part mouse antibody called a chimera. In clinical studies, their “humanized” drug, Rituxamab, cut tumor sizes in half. And when combined with other chemotherapies, it cured 79% of patients. The drug’s approval in 1997 led to the development of similar antibody-based therapies, some of which worked by killing cells directly (e.g. Rituxamab), others which slowed or stopped tumor growth by interfering with surface receptors on cancer cells, or some which better enabled the immune system to fight the disease.

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