A breakthrough cure for acute leukemia?

This week a group of scientists from Memorial Sloan-Kettering Cancer Center published what may be a genuine breakthrough in the search for a cure for cancer. The simple word "cancer" disguises what is really hundreds of diseases, most caused by genetic mutations that make a cell start replicating out of control.  The new study looks at a deadly form of leukemia, called B cell acute lymphoblastic leukemia, or B-ALL, and describes a radically new type of cancer therapy that uses genetic modification of a patient's own cells.

First a bit of background. Leukemias are cancers of the blood, which means they don't form solid tumors at all. Instead, the cancer cells circulate in the blood, going virtually everywhere in the body.  The blood has many cell types within it, including white blood cells or leukocytes, which is the origin of the word leukemia.  Lymphocytes are a type of white blood cell, and the two most common subtypes are called B cells and T cells.  B-ALL, then, is a cancer where a B lymphocyte has suddenly turned cancerous.

Scientists have developed chemotherapies to treat B-ALL, but if the first line of treatments fail and the cancer returns, the patient faces a very grim prognosis.  We really don't have any effective treatments at this point, and most patients die.

The new leukemia therapy is a technological tour de force.  The scientific team at Memorial Sloan-Kettering, led by Renier Brentjens and Michel Sadelain, genetically modified T cells from each patient so that these T-cells would target cancerous B cells.  The modified T cells use something called a "chimeric antigen receptor," or CAR, which they designed so that it would attach itself to a specific protein, called CD19, that sticks out of the surface of most cancerous B cells.  (This technique was invented by another group at Memorial Sloan-Kettering, led by Isabelle Rivière.)

What was amazing about this study is that in all five patients, their cancers virtually disappeared in just a few weeks.  As described in a The New York Times report, one of the sickest patients, 58-year-old David Aponte, saw his leukemia disappear in just eight days.  But we cannot know for certain yet if the therapy alone is a cure.  This is because the patients also had stem cell transplants within a few months after therapy, which may have helped eliminate any remaining cancer cells.  The therapy itself was temporarily very toxic, requiring close monitoring and steroid treatments to lessen the toxic side effects.  This may have been the reason that one patient died: the steroids may have hampered the therapy by destroying the genetically modified cells.

If this therapy were used as a first-line treatment of B-ALL, rather than in patients who have tried conventional therapy and relapsed, it might be even more effective (as the authors themselves suggest).  In particular, it is likely to be less toxic in patients who are at earlier stages of the disease and have fewer tumor cells in their blood.  Thus despite its promise, CAR T-cell therapy needs to be refined and tested further before we can declare it a success.

I'd like to make a final observation: this work, like almost all biomedical research in the U.S., was supported by the NIH, whose budget was just cut severely by Congress with its ill-conceived "sequester."  If we keep cutting biomedical research, we won't see many more breakthroughs like this one.  Even this dramatic result, promising though it is, needs more research to improve it and to test it on other leukemias, including chronic lymphycytic leukemia and non-Hodkins lymphoma, where it has already shown very promising results.

This leukemia treatment didn't just appear out of thin air.  It uses a technology that was invented four years ago, and that technology in turn is based on other discoveries that now make it possible to re-engineer a patient's own cells and turn them into a treatment.  Who knows where the next ten years will take us?   Now is the time to be increasing our investment in biomedical research.