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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Gum Disease and Cancer Risk

dental exam oral cavity white male head and neck oropharynx

New data supports the need to further investigate an association between periodontal disease and cancer risk.

Background: Previous studies have found periodontal disease is a risk factor for breast, oral, and esophageal cancers. Case-control studies have shown a link between tooth loss and the risk for esophagus and stomach cancers.

The Study: Investigators examined periodontal disease information in 65,869 women ages 54 to 86 at 40 centers in the USA. Mean age 68 years. Most were non-Hispanic whites with some college education. Participants answered this question: “Has a dentist or dental hygienist ever told you that you had periodontal or gum disease?”

The Results: This large prospective cohort study shows that postmenopausal women with a history of periodontal disease, including those who have never smoked, are at significantly increased overall risk for cancer as well as site-specific cancers, including lung, breast, esophageal, gall bladder, and melanoma skin cancers.Although periodontal disease and cancer share important risk factors (such as increased risk with increasing age and increased in smokers), this study showed that after adjustment for age, the risk of periodontal disease history and cancer persists regardless of smoking history.

My Take: This study adds to a growing body of evidence from smaller studies that link periodontal disease to total cancer risk. Oral hygiene is important not only in preventing tooth loss, but may have important implications for prevention of systemic diseases, including cancer. I’m Dr. Michael Hunter.

Cancer Epidemiol Biomark Prev. Published online 01 Aug 2017.

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Glowing tumor technology helps surgeons remove hidden cancer cells

Key Point: In a study from the University of Pennsylvania, surgeons were able to identify and remove a greater number of cancerous nodules from lung cancer patients when combining intraoperative molecular imaging (IMI) — through the use of a contrast agent that makes tumor cells glow during surgery — with preoperative positron emission tomography (PET) scans.

 

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Background: Pulmonary nodules are small growths in the lung. Doctors discover them in about 250,000 Americans each year. In 80,000 of those patients, the nodules are suspicious enough to warrant surgery. PET scans are standard before these procedures, and studies have shown they can detect malignancies in the nodules 90 percent of the time. But research has also shown these scans have limitations. They can’t usually show tumors smaller than a centimeter. They also can’t distinguish between cancerous growths and benign inflammatory diseases like infections. And importantly, scans taken before surgery don’t give surgeons real-time guidance once the procedure begins.

In order to get live imaging during surgery, Penn researchers used a near-infrared contrast agent called OTL38 that makes tumor cells glow. In past studies, they’ve shown it can detect malignant nodules as small as three millimeters — roughly one-third of the length of a shirt button. For this study, they combined PET imaging and IMI for 50 patients having surgery to remove lung nodules. All of the patients underwent a pre-operative PET scan within 30 days of their procedure. These scans identified a total of 66 nodules.

Results: During the operation, IMI identified 60 of the 66 previously known nodules, or 91 percent. In addition, doctors used IMI to identify nine additional nodules that were undetected by the PET scan or by traditional intraoperative monitoring. Between PET and IMI, a total of 75 nodules were identified. Researchers found that PET was accurate in determining if nodules were cancerous in 51 of them (68 percent). By comparison, IMI alone was accurate in 68 cases (91 percent).

IMI further improved diagnostics in 30 percent of the patients evaluated with this approach. In about 10 percent of patients, IMI helped surgeons find cancer that would have otherwise been missed by standard imaging like CT or PET.

“This shows the contrast agent is allowing us to remove more cancer from the patient than we would have with PET imaging alone,” said the study’s senior author Sunil Singhal, MD, the William Maul Measey Associate Professor in Surgical Research and director of the ACC’s Center for Precision Surgery.

This study lays the groundwork for future research involving OTL38. Researchers are currently evaluating this technology in a formal, multi-center trial that will be the first Phase II study of molecular imaging in the United States. They’re also exploring the effectiveness of additional contrast agents, some of which they expect to be available in clinic within a few months. They will also keep track of these patients to find out if these improved surgeries help patients live longer. These cancers also come back within five years in 25 to 30 percent of cases, so they hope to show these procedures lower that recurrence rate.

I’m Dr. Michael Hunter.


Story Source:

https://www.sciencedaily.com/releases/2017/07/170727115626.htm

 


Journal Reference:

  1. Jarrod D. Predina, Andrew D. Newton, Jane Keating, Eduardo M. Barbosa, Olugbenga Okusanya, Leilei Xia, Ashley Dunbar, Courtney Connolly, Michael P. Baldassari, Jack Mizelle, Edward J. Delikatny, John C. Kucharczuk, Charuhas Deshpande, Sumith A. Kularatne, Phillip Low, Jeffrey Drebin, Sunil Singhal. Intraoperative Molecular Imaging Combined With Positron Emission Tomography Improves Surgical Management of Peripheral Malignant Pulmonary Nodules. Annals of Surgery, 2017; 1 DOI: 10.1097/SLA.0000000000002382

 

Coming soon (within days): Free apps for Android and for iOS: My Breast Cancer.

How Exercise Reduces Dementia Risk

women walking exercise
Key Point: Physical exercise seems beneficial in the prevention of cognitive impairment and dementia in old age, numerous studies have shown. Now researchers have explored in one of the first studies worldwide how exercise affects brain metabolism. Their conclusion: Regular physical exercise not only enhances fitness but also has a positive impact on brain metabolism.

Background: Numerous studies have shown that physical exercise seems beneficial in the prevention of cognitive impairment and dementia in old age. Researchers at Goethe University Frankfurt explored how exercise affects brain metabolism. They examined the effects of regular exercise on brain metabolism and memory of 60 participants ages between 65 and 85 in a randomised controlled trial.

The Study: Researchers examined participants in the SMART study (Sport and Metabolism in Older Persons, an MRT Study) by assessing movement-related parameters, cardiopulmonary fitness and cognitive performance. In addition, they used magnetic resonance tomography (MRT) and magnetic resonance spectroscopy (MRS) to measure brain metabolism and structure.

Following this examination, participants rode an exercise bike three times a week over 12 weeks. The 30-minute training sessions were individually adapted to each participant’s performance level. Researchers then re-examined the participants to understand the effects of the physical activity on brain metabolism, cognitive performance and brain structure. The researchers also investigated to what extent exercise had led to an improvement in the participants’ physical fitness.

Results: As expected, physical activity influenced brain metabolism: It prevented an increase in choline. The concentration of this metabolite often rises as a result of the increased loss of nerve cells, which typically occurs in the case of Alzheimer’s disease. Physical exercise led to stable cerebral choline concentrations in the training group, whereas choline levels increased in the control group. Physical fitness also improved, with better cardiac efficiency after the training period. Overall, these findings suggest that physical exercise not only improves physical fitness but also protects cells.

I’m Dr. Michael Hunter.

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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 Minutes. Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

 



References:

  1. S Matura, J Fleckenstein, R Deichmann, T Engeroff, E Füzéki, E Hattingen, R Hellweg, B Lienerth, U Pilatus, S Schwarz, V A Tesky, L Vogt, W Banzer, J Pantel. Effects of aerobic exercise on brain metabolism and grey matter volume in older adults: results of the randomised controlled SMART trial. Translational Psychiatry, 2017; 7 (7): e1172 DOI: 10.1038/tp.2017.135
  2. https://www.sciencedaily.com/releases/2017/07/170721090107.htm

John McCain and Glioblastoma

US Senator John McCain recently had removal of an aggressive brain tumor known as glioblastoma multiform. It is a highly aggressive form of cancer that often returns quickly to the same spot, even with surgery, radiation therapy, and chemotherapy. McCain;s tumor was associated with a small blood clot above the Arizona Republican’s left eye, and surgeons removed it using a minimally invasive procedure. A statement from the senator’s office explains that imaging suggests that the neurosurgeon successfully removed the abnormality, at least the gross, measurable tumor.

What is Glioblastoma?

A brain tumor is a mass of abnormal cells that originated in the brain itself. GMB arises from supportive tissue (not the nerves themselves) in the brain (glial cells). Rarely, glioblastoma runs in families, but most individuals with GBM have no family history of the disease. While cancer can spread to the brain from other organs such as the lungs, GBM begins in the brain and only uncommonly spreads outside of it. For most individuals, we do not know the cause of GBM, but exposure to radiation to the brain is a known risk factor for the future development of cancer of the brain.

Next steps?

Following a recovery period of 3 to 4 weeks, patients typically proceed to radiation therapy (RT). The RT targets the tumor (or where it use to be) and often the surrounding edema (water) plus an inch or so. Often, those with GBM also have an oral chemotherapy known as temozolamide at the same time as radiation therapy (and sometimes after it). This approach of fractionated (for example, Monday through Friday for 6 weeks) radiotherapy plus oral chemotherapy is a category 1 recommendation of the National Comprehensive Cancer Network, a group of some of the top cancer treatment facilities in America. For those over 70, one may consider this approach versus a shortened course of radiation therapy versus chemotherapy with deferred radiation therapy.

In 2011, the Food and Drug Administration approached a portable medical device that generates low-intensity electric fields termed Tumor Treating Fields (TTF) for GBM. The use of this device (placed on the head) may yield results similar to chemotherapy, but with lower toxicity and improved quality of life.

Prognosis

Half of patients will survive beyond about 18 months. While 10 year survival is quite uncommon, it is possible. We need better treatments, and clinical trials are an important part of achieving this. 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 Minutes. Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.