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

 

New app for Android: My Breast Cancer by Dr. Michael Hunter

 

Should doctors prescribe exercise?

“Although the data vary by different cancer types, there is a consistent trend suggesting that moderate daily exercise has a beneficial effect on preventing certain cancers. If you are a reasonably healthy adult, your should exercise regularly.” 

Let’s look at the relationship of exercise and selected cancers. The American Society of Clinical Oncology (ASCO) has done a nice job of summarizing:

Breast Cancer

While the amount of risk reduction varies among studies (20-80%), most suggest that 30 to 60 minutes of moderate to high-intensity exercise per day lowers breast cancer risk. Women who are physically active throughout their life appear to benefit the most, but those who increase physical activity after menopause also fare better than inactive women.1

Colon Cancer

Research suggests that people who increase their physical activity can lower the chance of developing colon cancer by 30 to 40% relative to sedentary adults.1,2 A decrease in colon cancer risk can be achieved regardless of body mass index (BMI) and people who are most active benefit the most. There is insufficient evidence of a protective effect of physical activity on the risk of rectal cancer (a protective effect was seen in some case-control studies, but not in cohort studies).3

Endometrial, Lung and Ovarian Cancer

A handful of studies have suggested that women who are physically active have a 20-40% reduced risk of endometrial cancer compared to those who don’t exercise.1 Higher levels of physical activity seem to also protect against lung cancer (up to 20% reduction in risk), particularly among men.1Although less consistent, research suggests that physical activity possibly reduces the risk of ovarian and prostate cancer.

What about Other Cancers?

While observational data on the benefits of exercise for prevention of the types of cancers listed above are fairly consistent, evidence of the effects of exercise on prevention of any other type of cancer either is either insufficient or inconsistent.2,4

Prostate Cancer

Prostate cancer is one disease in which the data are not consistent, however prostate cancer is a heterogeneous disease and risk factor associations for total non-aggressive disease are different from aggressive / lethal disease. Most population based studies show similar findings, with little effect of exercise on overall incidence of prostate cancer but lower risk of aggressive prostate cancers for those with the highest levels of VIGOROUS activity (rather than any type of activity). In the Health Professionals Follow-up Study men 65 years or older who engaged in vigorous physical activity, such as running, jogging, biking, swimming or tennis at least three hours per week  had a 67% lower risk of advanced prostate cancer and 74% lower risk of fatal prostate cancer.5

Conflicting data for other malignancies

For example, one recent study found no association between physical activity and risk of developing gastric, rectal, pancreatic, bladder, testicular, kidney and hematological cancers.4 In contrast, a pooled analysis of data from prospective trials with 1.4 million participants found that physical activity was linked to lower risk of 13 cancers: esophageal, lung, kidney, gastric, endometrial, myeloid leukemia, myeloma, colon, head and neck, rectal, bladder, and breast.6Interestingly, leisure-time physical activity was associated with a higher risk of melanoma (presumably due to time spent outdoors) and prostate cancer, although it is not clear from these data whether that association was with nonaggressive or aggressive prostate cancer.

While we wait for confirmation and clarity on the role of exercise in preventing all the 200+ types of cancer – should doctors prescribe exercise? The answer is simple: yes, because evidence of the protective role of exercise is already strong for some of the most common cancers.

References

  1. Lee I, Oguma Y. Physical activity. In: Schottenfeld D, Fraumeni JF, editors. Cancer Epidemiology and Prevention. 3rd ed. New York: Oxford University Press, 2006.
  2. Slattery, ML. Physical activity and colorectal cancer. Sports Medicine 2004; 34(4): 239–252.
  3. Pham NM, et al. Physical activity and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2012 Jan;42(1):2-13.
  4. Friedenreich CM, Neilson HK, Lynch BM. Eur J Cancer. State of the epidemiological evidence on physical activity and cancer prevention. 2010 Sep;46(14):2593-604.
  5. Giovannucci E, Liu Y, Leitzmann MF, et al. A prospective study of physical activity and incident and fatal prostate cancer. Arch Intern Med. 2005; 165(9):1005-1010.
  6. Moore SC, Lee IM, Weiderpass E, et al. Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults. JAMA Intern Med. 2016 Jun 1;176(6):816-25.
  7. http://www.asco.org/about-asco/press-center/asco-resources-media/cancer-perspectives/should-cancer-doctors-prescribe?et_cid=38723632&et_rid=463715101&linkid=Read+more

I’m Dr. Michael Hunter. Of course, the disclaimer: Do not begin an exercise program without input from an appropriate medical professional. Many can simply start with a brisk walk for 30 minutes daily, 5 days per week. Have a wonderful day!

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