Tuesday, October 18, 2016

T-Cell Cancer Therapies: Greater Scrutiny Required

Cancer Research

Dividing Lymphoma Cells: The thinking is that these can be destroyed by CAR-T therapy.
Image Credit: Steve Gschmeissner; SPL
Source: Nature

An article, by Hedi Ledford, in Nature shows how difficult it is to meet the public expectations for emerging new therapies to treat cancer. One of the most promising (and perhaps over-hyped) is an immunotherapy, where the body's T-cells are used to fight cancer. While it has been successful in particular cancers, it has also resulted in human deaths in others.

The central issue is how to both effectively and safely use such newer therapies, which don't have the proven track record of conventional cancer therapies like chemotherapy, which have been around for decades. Oncologists know all of chemo's side effects. This is hardly the case with the newer therapies that use the body’s T-cells.

One such example is known as CAR-T, which is an acronym for chimeric antigen receptors T-cell therapy.  The National Cancer Institute describes it in the following way: “After collection, the T cells are genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARs). CARs are proteins that allow the T cells to recognize a specific protein (antigen) on tumor cells. These engineered CAR T cells are then grown in the laboratory until they number in the billions.”

In “Safety concerns blight promising cancer therapy” (October 12, 2016), Ledford writes:
But progress of the therapy, called CAR-T, has been marred by its toxicity; several deaths have been reported in clinical trials. Even as the first company readies its application to the US Food and Drug Administration (FDA) — expected by the end of the year — researchers are hard at work to make the supercharged T cells safer.
Doing so is crucial to expanding the use of the therapy to more people, says Anthony Walker, a managing partner at Alacrita, a consulting firm in London. “Right now it is heroic medicine,” he says — a gruelling treatment deployed only in people for whom all else has failed. “Patients are taken sometimes to within an inch of their lives.”
Most CAR-T procedures begin by harvesting a patient’s white blood cells and sifting out the T cells. Those T cells are engineered to recognize cancer cells, and then infused into the patient, ready to do battle. The approach has shown remarkable success against leukaemias and lymphomas: in one study, all traces of leukaemia disappeared in 90% of the patients who received the treatment (S. L. Maude et al. N. Engl. J. Med. 371, 1507–1517; 2014).
A promise is only as good as its ability to be fulfilled. The jury is still out on immunotherapies like CAR-T, and it will take time. Even if the FDA starts approving such therapies, it will take years of real-life data to see if it is indeed effective and safe for the majority of patients. It is true that all therapies have some risk, but it ought to be an acceptable risk, This is the primary role of the FDA, is it not?

During my last visit, when I questioned my oncologist, who is also a medical researcher, on whether immunotherapy was ready to replace conventional therapies like chemotherapy, he said not yet, adding that there was a great deal of hype surrounding much of cancer research announcements—where it is difficult to ascertain fact from fiction. Well, if truth be told, so much and too much in America is bathed in hype, notably if there is money or commercial investment involved.

There is a valley of difference between hype and hope, where the latter is based on bettering the human condition for the greatest number of people. One wonders how important patient interests are when compared to others that have more tangible rewards. Let’s hope that the FDA does not rush things just to line the pockets of a few. It would be far better if they are guided by the ethical principals of beneficence.

For more, go to [Nature]