labletters

Blogging about biomedical science and engineering research with an emphasis on public health and education.

Anti-Cancer Therapy Now Features a Safety Switch

Self-destruct signal designed to keep patients safe

Some of today’s most exciting advances in medicine involve taking a patient’s own immune cells, tweaking them in the lab, and returning them to the patient to effectively treat disease. A high-profile example of this was highlighted in the New York Times in 2011, in which William Ludwig was the first patient whose leukemia was cured using his own immune system.

This treatment strategy is not without risk, however; Mr. Ludwig and others receiving engineered T cells can experience fever, low blood pressure and other toxicities that have unfortunately led to some patient deaths. Another concern is that the cells could themselves turn malignant. To prevent these serious events, Bellicum Pharmaceuticals, Inc. has announced the first clinical trial of a  Chimeric Antigen Receptor (CAR) T Cell therapy with an integrated safety switch that can wipe out the T cells if they endanger the patient.

The “CaspaCIDe” safety switch system is pretty slick – the immunotherapy cells include an inducible Caspase-9, the pathway which initiates the steps toward cell death (apoptosis). If a patient experiences serious adverse side effects to the therapy, a small bio-inert molecule can be administered to start this Caspase-9 signaling and the CAR T cells proceed to rapidly commit suicide.

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This suicide switch is an important step forward in being able to ensure the safety of any cellular therapy in the future. The CaspaCIDe system fills the need to quickly shut down the engineered cells in the event of an emergency. With so many cell-based immunotherapies in development, we could be hearing a lot more about this safety strategy in the future.

 

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Vaccine Series: Pertussis/Whooping Cough

The dilemma with effective vaccines is that we forget the terrible diseases they prevent. The “Vaccine Series” discusses the diseases to help us remember why vaccines are critical to public health.

“Whooping cough” is one of the latest diseases to regain headline notoriety. Technically called pertussis, a highly contagious bacterial disease, whooping cough causes the upper respiratory tract infection known for the violent coughing and the “whooping” sound that is heard when a young patient tries to take a deep breath. This disease typically lasts for 6 weeks, providing for its rapid spread through a population when a patient coughs up the bacteria. Before vaccines, the whooping cough was most common in infants and young children, and families dreaded the permanent disability and even death that could occur in infants.

When the pertussis vaccine was first widely recommended in the 1940s, childhood deaths due to the disease dropped dramatically. Unfortunately, controversy over the connection between autism and routine vaccines have led parents to increasingly resist recommendations to vaccinate their children. (Follow-up studies have shown that autism is not a side effect of routine childhood vaccinations.) The failure to vaccinate children is extremely dangerous for the infants who have not yet received their full series of DTaP vaccinations.

The DTaP vaccine is for kids younger than 7 years of age, and it provides protection against diphtheria, tetanus, and pertussis. Because the first dose of DTaP vaccine is recommended at 2 months of age, babies younger than this are most at risk for preventable infant mortality. Children whose parents declined to have them immunized against pertussis have been found be 23 times more likely to get whooping cough compared to fully immunized children.

Areas experiencing outbreaks of whooping cough, such as in the northwest, have reached a tipping point in the loss of herd immunity. Herd immunity refers to the community-wide protection against disease by large percentage of vaccinated individuals. However, when enough people are not protected by vaccines, sensitive groups such as infants, pregnant women, or immunocompromised individuals are put at greater risk for the disease. Complicating the issue is the fact that pertussis vaccines have a duration of protection between five to ten years. For this reason, Tdap booster shots are recommended for adults and may be requested by parents of small children.

Vaccination against pertussis is critical in preventing the widespread outbreak of the disease. In the context of a community, it is just as important for adults to be protected as it is for children to receive the recommended vaccine series. When more people are protected, the disease is less likely to spread to sensitive groups, and the overall risk of infant mortality is lowered. If you would like to learn more about which vaccine is right for you and when it is recommended, see this summary of pertussis vaccine recommendations provided by the CDC.

Is Germophobia Making Us Sick?

We all know the drill: wash your hands after using the bathroom, wash them before eating, and again after doing anything that gets them dirty. We use antibacterial soap and disinfectants religiously. But has our obsession with killing germs gone too far?

The emergence of scary super bugs such as the antibiotic-resistant MRSA would certainly point to our over usage of antibiotics and antibacterial products. From a biology perspective, a certain number of bacteria will always manage to obtain a genetic advantage that allows them to survive the antibiotic onslaught. With continued use, we’re essentially breeding these resistant bacteria.

But not all germs are bad! In fact, bacterial cells in our body number at least 10 times the amount of human cells! How is this even possible? In addition to their small size relative to our cells, a great number of bacteria exist unseen in our digestive tract. These microbes help us digest our food, make vitamins to help keep us healthy, and – importantly – play a key role in the development and maintenance of our immune systems. Referred to as the “microbiome,” this is currently a hot topic in science.

Yep, the microbes that normally populate our bodies and digestive tract help train our bodies to detect and also protect us from the real pathogens that actually pose a danger to our health. Antibiotic usage can dramatically reduce the population of the good guys in our gut, so this is another reason to use antibiotics only when they are truly necessary. Inflammatory bowel diseases such as Crohn’s Disease, ulcerative colitis, and irritable bowel syndrome have also been linked to abnormal microbe populations in the gut, possibly in connection with our overly sanitary lifestyles and antibiotic usage.

To illustrate a similar message, a professor in one of my classes had a student toss one of her Cheetos on the floor at the beginning of the lecture.  During the lecture, he stressed the importance of letting kids play in the mud and getting exposure to all sorts of germs to help their immune systems develop robustly. After teaching the whole hour and a half, we had mostly forgotten about that lonely Cheeto… The prof didn’t – he marched over, picked up the Cheeto and ate it right off the floor. I reflexively thought “yuck!” even though it drove home the point – some of our sanitary habits are completely unnecessary and sometimes even harmful.

Obviously, don’t nix your hand washing routine – this is how we prevent the spread of the real pathogens that make us sick. But most people don’t actually need antibacterial soap. Hand washing with regular soap and warm water, with the right technique, is more than adequate for most situations. Alcohol-based hand sanitizers are antibacterial without using antibiotics, so they’re completely appropriate when a sink is not available.

Bottom line, the friendly bacteria that are normally present in our bodies and environment are critical to our health and well-being. We all have to get over (some of) that ick factor that we’ve been trained to have since germs were first discovered.


 

Additional References

The indigenous gastrointestinal microflora

The gut microbiota: challenging immunology

Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era


Science PR? Challenge ACCEPTED!

Science outreach has been getting a lot of attention these days, thanks to the recently published PLoS ONE article that looks at why scientists are stuck in the “ivory tower.” Frankly, some scientists are just ill-equipped to talk to regular people, and I haven’t met anyone yet who chose a career in science because of his or her supreme writing skills. That said, in my graduate education thus far, I have found that the most successful faculty members at BCM are excellent communicators (recently in the news Lynn Zechiedrich, for one).

The subject is gaining momentum… I mean, just days after I made the decision that I wanted to start a science blog, Soapbox Science (a blog by the pinnacle science journal Nature) started a series on how to engage the public in science discussions.

So it’s now well established that we scientists need to do a better job of reaching out to the public to share what we do and why it is important. Annnnd to share it in a way that non-scientists can actually understand.  In the words of the legendary Barney Stinson, “Challenge accepted!”

What’s my interest in this? For starters, I have a burning desire to talk about certain science and health issues that I feel get misrepresented, misunderstood, or flat-out ignored in the general media. I also want to help people like my family (Hi Mom!) and friends understand what it is that I do. Fundamentally, I have a huge passion for both science and education, and starting a science blog seems like a good way to follow my passion on my journey to a PhD.

Some good reads to tide you over until next time…

Science has a PR Problem
Women researchers more likely to conduct outreach