CAR T Cells as “Living Drugs”

“Incredibly exciting” is how experts are describing the new development with chimeric antigen receptor (CAR) T cells, as the first of these novel therapies approaches the market.

“Living Drugs”

The treatment product is made individually for each patient. After blood is taken from the patient, it undergoes a process that involves extracting immune system T cells, subjecting the cells to CAR cell engineering, and then infusing the engineered T cells back into the patient. The engineering changes the T cell in two ways. First, it adds a receptor that targets the CD19 antigen that is found on most leukemia cells. When the cells are returned to the patient’s body, they home in on this antigen, latch on, and destroy the leukemia cell. Second, the process inserts a viral vector mechanism into the cells that, once the cells have latched onto the leukemia cell, triggers these T cells to expand and proliferate, so that they seek out and destroy all the remaining leukemia cells.

Because they grow and expand in the body and then lie dormant, CAR T cells have been described as “living drugs.” It is not clear whether CAR T cells will also last a lifetime or whether will they gradually disappear over decades. It is also not clear how long immunosurveillance may be needed, he said. While policing the blood, these cells wipe out any leukemia B cells that may reappear, but there can be a downside. In some patients, this has also led to depletion of healthy B cells, a condition known as known as B cell aplasia. “This is not a major problem, at least not so far,” commented one expert, because this deficiency can be corrected by giving immunoglobulin supplements, in some cases long-term.

The worst of the side effects occur within a week or two of infusion, when the cells are expanding and attacking the leukemia. Some of the side effects can be very severe, even life-threatening. The two most concerning side effects are cytokine release syndrome, which was severe in about half of the patients in the pivotal trial, and neurologic toxicity, which developed in nearly half of the patients (44%). Because there can be severe side effects, patient care needs to be overseen by clinicians with experience in this field, and suitable facilities are required. Patients may need to be treated in the intensive care unit, for example, and some patients may need to undergo intubation.

Having industry involvement has streamlined a complicated production process and has shortened the manufacturing time. Whereas patients at the beginning of the clinical trial needed to wait 44 days between giving blood and undergoing CAR T-cell infusion, the process now takes only 22 days from “vein to vein,” the drug company Novartis reports. For the future, there is hope that it may be possible to make “off the shelf” products that would require no waiting time. There is also work underway to incorporate a “genetic switch” into the CAR T cell, which would make it possible to “turn off” the therapy by taking another drug. This could be useful when side effects become very severe, he suggested.

There is a tremendous amount of work ongoing involving other blood cancers, all of which appear suitable to this approach. There is also hope that the therapy could be made to work against solid tumors. This first product that is heading to market is just the tip of the iceberg. I’m Dr. Michael Hunter. Medscape did a great job reporting it, and I thought I’d share this news with you.

Reference: http://www.medscape.com/viewarticle/882968#vp_3

 

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Allergies and Hematologic Cancer Risk: Is There a Link?

young white woman blowing nose allergy

Women with airborne allergies could be at higher risk for hematologic malignancies than women without allergies, researchers contend.

The Study: Data from a prospective cohort study of more than 66000 older adults in Washington state (USA) found that women with any airborne allergen had a 1.47x increase in risk for a hematologic cancer. In addition, women who hit the allergy trifecta of sensitivity to plants, grass, and trees had a 73% greater chance of developing a mature B-cell lymphoma or related disorder.

Overall, men were more likely than women to develop a hematologic malignancy, but the risk in men was not significantly associated with allergic status, write Mazyar Shadman, MD, MPH, and colleagues from the Fred Hutchinson Cancer Research Center in Seattle.

“For other cancers, the idea long ago was that if you have allergies, your immune system is kind of hyperactive, and that should lower your risk for other cancers,” he explained. However, he added, “for hematologic cancers, you could go either way, because immune surveillance would be good but, if you have allergies, that means that cells are dividing more to mount the immune response, increasing the chance of mutations,” offers Richard G. Stevens, PhD, professor of cancer epidemiology at the University of Connecticut Health Center.

My Take: While allergies may increase the risk of cancer of the blood/lymph system, it may lower the risk of other cancers, including of the head and neck. Although the study was large and had comprehensive baseline data, it was limited by its reliance on self-reporting of allergies and by the inclusion of data only on current allergies, rather than allergic history. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Am J Hematol. 2013;88:1050-1054. Abstract