Cancer care has seen its share of false dawns in recent years, with many new drugs failing to live up to their early promise. But now there’s great excitement over so-called “superblood” — red blood cells that have been chemically modified to deliver cancer-killing drugs like L-asparaginase, an enzyme that blocks the nutrients cancer cells use to grow and multiply.

"The strategy is very clever," said Dr. Philip Low, a professor of chemistry at Purdue University and director of the university's Center for Drug Discovery.

Some researchers believe that doses of superblood could work against potentially deadly malignancies that are hard to treat with existing therapies. These include triple-negative breast cancer and pancreatic cancer as well as cancers of the liver, ovary, and colon.

“The idea is that some of these cancer cells have become extremely reliant on nutrients in the bloodstream for their metabolism,” said Dr. Vladimir Muzykantov, a professor of pharmacology at the University of Pennsylvania and a member of the advisory board of EryDel of Milan, Italy, one of the firms that is developing superblood. “If you load red blood cells with enzymes which destroy these nutrients, then you help to starve cancer cells by interrupting their supply.”

Longer-lasting activity

L-asparaginase was approved as a treatment for certain cancers in the late 1970s. But it’s proven to be only marginally effective, in part because it remains active in the body only for a matter of days.

“Asparaginase is not of human origin,” said Dr. Hidde Ploegh, a professor of immunology at Harvard Medical School and a member of the scientific advisory board of Boston-based Rubius Technologies, another firm that is working on superblood. “This means our immune system makes antibodies against it, which neutralize or eliminate it from the circulation. By encapsulating it within a red blood cell, you shield it from the immune system, and keep it performing.”

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Studies show that L-asparaginase delivered by superblood continues to work in the body for up to three weeks.

Bringing superblood to market

Superblood research has advanced rapidly in recent months.

Rubius Therapeutics has raised close to a quarter of a billion dollars in investor funding to support clinical trials of superblood. EryDel and Erytech Pharma of Lyon, France are awaiting approval of superblood for the treatment of acute lymphoblastic leukemia. Erytech’s product could be approved for use in Europe in 2020 and gain FDA approval for use in the U.S. as soon as 2021.

Though all three companies are working to develop L-asparaginase superblood, they're taking different approaches.

Erytech and EryDel use red blood cells taken from a blood bank. The cells are soaked in a solution to make their outer membranes permeable and then exposed to a solution of asparaginase. The resulting asparaginase-laden superblood is given to patients twice a month for a period of six months or longer.

Rubius, meanwhile, is developing superblood made using a patient’s own cells. “The advantage is that what you transfuse into the patient more closely resembles what they already have in their circulation, which has fewer risks,” Ploegh said.

Beyond cancer

Superblood is known to be effective against acute lymphoblastic leukemia, and we should know within the next five years whether it works against other deadly cancers. But even if superblood fails to live up to its promise as a cancer therapy, it could find use against other illnesses, including stroke and autoimmune diseases like multiple sclerosis.

“There’s all kinds of applications for using these cells to carry drugs ranging from preventing clots accruing in the cerebral arteries which supply the brain, to proteins which bind to the cells and can be used to turn the body’s immune response off,” Muzykantov said. “I really believe that the future potential of drug delivery using red blood cells is huge.”

But Dr. Farhad Ravandi-Kashani, a hematologist-oncologist at the University of Texas MD Anderson Cancer Center, offered a more cautious assessment of superblood's therapeutic potential. "If this treatment turns out to be effective and less toxic as it is reported to be, it will be useful," he said." But right now, until we have more data, the potential, I think, is limited only to hematologic malignancies, and in particular, acute lymphoblastic leukemia."

EDITOR'S NOTE: This story was updated to include comments from Dr. Low and Dr. Ravandi-Kashani and to indicate that Dr. Muzykantov is affiliated with EryDel and that Dr. Ploegh is affilated with Rubius Therapeutics.

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