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antibody binding

A New Type of Cancer Immunotherapy

A newly emerging type of cancer immunotherapy uses bispecific antibodies. These drugs attach to both immune cells and tumor cells thereby facilitating destruction of the tumor. They are called bispecific as they bind to a unique surface protein, CD3, on an immune T cell and to a antigen marker on a tumor.

Although bispecific antibodies have been studied for decades, the field was slow to develop due to difficulties in designing and producing the drugs. Those problems are now rapidly being overcome. The field continues to evolve with many new designs of bispecific antibodies being prepared. A major advantage of bispecific antibodies is that they can be mass produced in advance.

Bispecific antibody therapy joins other well-established methods of immunotherapy. CAR T cell therapy involves the use of bioengineered drugs. In this approach, T cells are separated from a patient’s blood, and a specialized receptor gene is inserted. The CAR T cells are then multiplied in the laboratory and reinserted into the patient. The CAR T cells have enhanced ability to hone onto cancer cells and destroy them.  CAR T cells, however, must be prepared for each patient, an expensive and slow process.

Another important immunotherapy treatment involves the use of checkpoint inhibitors.  Immune checkpoints are signals used by the immune system to control an immune response. After the immune response has completed its task, checkpoint inhibitor proteins shut down its activity to prevent the immune system from destroying normal tissue. Cancer cells can develop the means to stimulate these proteins to prevent the immune system from attacking the cancer. Checkpoint inhibitor drugs known as monoclonal antibodies can block this action.

All three immunotherapies have their limitations, so many researchers now believe that the most effective therapy could involve using them in combination.

Reference

http://science.sciencemag.org/content/368/6494/930

In a recent article in the New York Times, (https://www.nytimes.com/interactive/2020/04/30/opinion/coronavirus-covid-vaccine.html)

Stuart Thompson provided sobering information regarding a proposed timetable to develop a COVID-19 vaccine. Although the most optimistic estimate provided by top health officials is to develop a vaccine in 12-18 months, typically vaccine development requires at least a decade.

Why does vaccine development take so long? A vaccine must be proven to be safe and effective to be approved for use by the FDA. Achieving these high standards can take a long time. The development of a vaccine begins with academic research. After lab studies, clinical studies with a few humans begins to evaluate toxicity. Phases II and III follow with increasing numbers of patients. Finally, a New Drug Application is submitted to the FDA for approval. After approval, pharmaceutical companies face other major challenges, including scale-up for manufacturing, often requiring building a new factory to accommodate specific needs for the vaccine. Also, distributing the vaccine to millions of people would be a logistical challenge.

Fortunately, developmental research on COVID-19 can be shortened due to previous research on coronaviruses. The timeline could be advanced by starting up manufacturing capability even before approval of the vaccine, which could entail great risk for a pharmaceutical company. Most of the vaccine development on COVID-19 uses the new DNA and mRNA vaccines which provide many advantages over older technologies, including inherently better safety and more rapid production.

The article makes it clear that while waiting for a vaccine, the best immediate hope would be for the development of effective treatments. A vigorous search is underway evaluating current therapies for other conditions to see if they could be safe and effective against COVID-19. As of this writing, The FDA has approved the emergency use of remdesivir for treatment of patients who require a ventilator. Clinical studies have shown that remdesivir can reduce the recovery time by four days and can also reduce the mortality rate. These studies are promising but indicate that the search for effective treatments is far from over.

I will discuss DNA and mRNA vaccines in future articles and how they can be useful against cancer.

 

Better off Bald book cover

Review of Better off Bald

Better off Bald is an extraordinary book by Andrea Wilson Woods describing the journey she took with her younger sister Adrienne, who was diagnosed with liver cancer. The book serves as a profound statement on how cancer affects both patients and caregivers. Andrea carries on the legacy of Adrienne through nonprofit organizations she founded to provide awareness and education related to cancer.
Better off Bald is written as a journal, with each chapter representing a certain number of days after Adrienne’s diagnosis. Each chapter begins with a journal entry written by Adrienne. These entries provide insight into Adrienne’s character. Andrea brings the reader into her thought processes as she copes with the progression of Adrienne’s cancer. She writes in short sentences often with contradictory viewpoints reflecting a person in the panic of the moment. Interspersed within each chapter are remembrances of the lives together of the two sisters. Andrea obtained custody of her sister after her mother was no longer capable of taking care of Adrienne.
Andrea’s book is essential reading for anyone serving as a caregiver for a loved one. Beginning with the shocking and unexpected diagnosis of advanced cancer in Adrienne, Andrea has to navigate through the world of hospitals and doctors, keeping up with all the medications and daily crises in Adrienne’s condition. Although Adrienne’s condition appears hopeless, Andrea conducts extensive research on liver cancer and becomes very knowledgeable on the subject. However, doctors treating Adrienne do not find the alternate treatments found by Andrea to be viable alternatives.
The profile of Adrienne shows a spirited young woman who is a fighter. The diagnosis of cancer served as a wake-up call to develop strength of character and an overall positive approach to life. Instead of giving in to depression, Adrienne looks forward to new experiences and events.
The loss of Adrienne’s hair during treatment inspired the title, Better off Bald. In this way, Adrienne’s inner beauty can better come forth, not hidden by hairstyles as a means of self-expression.
The photos in the book very nicely complement the text; Adrienne is always smiling and in good spirits. Adrienne’s favorite photo sees herself as an elegant mannequin instead of wasting away from disease. Adrienne is beaming during her meeting with her idol, Dave Navarro. The “View from Adrienne’s grave” at the end of the book was particularly touching as Adrienne was fond of the Hollywood sign.

Molecular pathways in cancer

Treating Cancer with Immunotherapy and Targeted Therapy

Treating cancer has always been a major challenge. Although great strides in treatment have taken place in recent years, all too often current treatments are less than effective, or patients relapse. Newer methods of cancer treatment, namely targeted therapy and immunotherapy, have generated great excitement in the scientific community. These newer methods of cancer treatment hold promise for patients who otherwise may have few options. Also, in the case of immunotherapy, responses to treatment can be maintained even after a cycle of treatments is complete.

This book discusses all the basics of cancer for the general reader, including characteristics and development of cancer, diagnosis, and classification. Standard methods of cancer treatment are discussed, including surgery, radiation, chemotherapy, and hormone therapy. The rationale and development of targeted therapies are presented. The immune system as it relates to cancer is explained, followed by the presentation of the main categories of immunotherapy, including checkpoint inhibitors, adoptive cell therapy, and cancer vaccines.

Published by Mercury Learning and Information

Arcade Gaming

Is Video Game Addiction a True Mental Disorder?

Is Video Game Addiction a True Mental Disorder?

The World Health Organization has included the condition “gaming disorder” in the latest 11th edition of its International Classification of Diseases (ICD-11). This inclusion follows the classification by the American Psychiatric Association (APA) of “Internet Disorder” as a “condition for further study” in its latest Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The ICD and DSM are major diagnostic manuals for mental disorders. As a result of collaborations between the organizations, the classification systems described in the publications have converged strongly in their latest revisions.

The APA is hesitant to call Internet Disorder as an “official” disorder; as such a classification would have important implications for physician diagnosis and treatment as well as for insurance claims. The WHO classification is already official for that organization.

According to the WHO, gaming disorder can include: impaired control over gaming; 2) increasing priority given to gaming to the extent that gaming takes precedence over other life interests and daily activities; and 3) continuation or escalation of gaming despite the occurrence of negative consequences. For gaming disorder to be diagnosed, the behavior pattern must be of sufficient severity to result in significant impairment in personal, family, social, educational, occupational or other important areas of functioning and would normally have been evident for at least 12 months.

The WHO recognizes that gaming disorder affects only a small proportion of people who engage in digital- or video-gaming activities. However, the inclusion of gaming disorder in ICD-11 will result in the increased attention of health professionals to the risks of development of this disorder and, accordingly, to relevant prevention and treatment measures. Addiction is usually associated with the taking of drugs or other substances (substance abuse), but an understanding of the disorder has been expanded to include behaviors not involving substances, such as gambling addiction.

A group of scholars has taken issue with the WHO’s classification of gaming disorder. Their contention is that the WHO and the APA find a unique disorder in what is a normal recreational activity (video gaming). The scholars argue that the wrong criteria are used to diagnose gaming addiction (neglecting other activities in the gamer’s daily life). They feel that problems with video gaming could be the result of a preexisting mental health disorder.

This issue is related to larger problems of classifying mental disorders. Classification systems are often based on the assumption of assigning categories with distinctive characteristics. In the case of mental disorders, the characteristics shown in many categories can show overlap. In other words, it can be difficult to classify mental disorders as distinct entities. Mental disorders are largely based on observable signs and patient-reported symptoms rather than by their underlying causes.

Van Den Brink replied to the scholars’ paper agreeing that there is nothing inherently wrong with video gaming and that it can be just another recreational activity.  However, he notes that, just like other activities, gaming becomes a problem when the person loses control over it, and it replaces other important activities.

What should the gamer or concerned family and friends do?

Gamers, as well as concerned family and friends, should be alert to the extent that gaming activities could be impairing their daily activities. Only a small proportion of gamers develop a truly addictive behavior, so people around the gamer should not become unduly alarmed. Many gamers with disorders can overcome their problems without professional help. The ICD-11 and DSM-5 classifications of gaming addiction provide guidelines to professionals, but they still use their clinical jjudgmentfor diagnosis and treatment of the condition.

References

  1. Aarseth, Espen, et al. “Scholars’ open debate paper on the World Health Organization ICD-11 Gaming Disorder proposal.” Journal of Behavioral Addictions 6(3), pp. 267–270 (2017) https://akademiai.com/doi/pdf/10.1556/2006.5.2016.088
  2. Clark, Lee Anna, et al. “Three Approaches to Understanding and Classifying Mental Disorder: ICD-11, DSM-5, and the National Institute of Mental Health’s Research Domain Criteria (RDoC)” Psychological Science in the Public Interest, 18(2) pp.72–145 (2017) http://journals.sagepub.com/doi/pdf/10.1177/1529100617727266
  3. Sarkis, Stephanie. Internet Gaming Disorder in DSM-5. Psychology Today

https://www.psychologytoday.com/blog/here-there-and-everywhere/201407/internet-gaming-disorder-in-dsm-5

  1. Van den Brink, Wim. “ICD-11 Gaming Disorder: Needed and just in time or dangerous

and much too early?” Journal of Behavioral Addictions 6(3), pp. 290–292 (2017)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700715/

  1. World Health Organization. Gaming disorder.

http://www.who.int/features/qa/gaming-disorder/en

 

 

 

Video Game Addiction

Video game addiction is a term that should be used with care. When video gaming disrupts multiple areas of a gamer’s life, it may more properly be called a disorder or addiction. Although only a small percentage of video gamers experience addiction, in terms of total numbers it is significant.

Video Game Addiction addresses the question of clinical addiction as well as other topics; including the nature of video gaming, the treatment and recovery from video game addiction, and some beneficial effects of video gaming. The book can be obtained from Mercury Learning and Information.

 

Asthma

Asthma is a very serious, widespread, and growing problem in the U.S. Asthma affects over 24 million Americans, and its prevalence has increased 12% in the last decade. This book is designed to be a comprehensive background on asthma for the general public. The latest developments in the understanding of asthma and its relationships to allergies and other conditions are presented. A broad range of treatments for asthma are available or under development. The book is published by Mercury Learning and Information, and is available in paperback or as an e-book.

Advances in Understanding Itch

Everyone experiences itching. The sensation of Itching can result from something as innocuous as an insect bite to a more serious chronic debilitating form that can be difficult to treat.

Recent advances in understanding the itching process may help in developing more effective treatments to control itch. It has been known for some time that an irritation to the skin caused by a mosquito bite or poison ivy, for example, results in an immune response by the body releasing histamine. Histamine binds to and activates the TRPV1 receptor found on the endings of sensory nerves in the skin, resulting in the transmission of a nerve signal to the brain and the sensation of itch. This understanding is the basis for the use of antihistamines for treating itch. Realizing that not all itch conditions are helped by histamines, researchers set out to learn more about the causes of itch.

A few years ago, another itch receptor (TRPA1) was discovered that is activated by substances other than histamine. Is there a link between itch and pain?   The findings indicate that neurons containing only the TRPV1 receptor process pain sensation. On the other hand, neurons containing either the TRPV1 receptor or the TRPA1 receptor can transmit itch signals. The results also suggest that pain circuits can inhibit itch circuits, so only one signal is sent at a time—explaining why pain and itch rarely happen simultaneously.

Should you scratch your itch? Apparently scratching an itch has an evolutionary basis–to remove threatening bugs and plants. Scratching stimulates nerve endings in the spinal cord to release natural painkilling molecules. Scratching may bring temporary relief, but continued scratching may injure the skin leading  to a greater sensation of itching.


References

1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. “Investigating the Causes of Chronic Itch: New Advances Could Bring Relief.” Spotlight on Research 2014.

http://www.niams.nih.gov/News_and_Events/Spotlight_on_Research/2014/chronic_itch.asp

2. Piergrossi, Joseph. “Untangling the Source of Ouch and Itch.” National Institutes of Health, June 12, 2013. NIH article on Itch

https://publications.nigms.nih.gov/insidelifescience/untangling-ouch-itch.html

3.Sutherland, Stephani. The Maddening Sensation of Itch. Scientific American, May 2016, p. 39-43.

A New Direction-  This posting concludes my blog on “keeping abreast on developments in medical research” in order to devote more time to writing a new book on asthma. The blog page on my website will be replaced by a Resources page providing brief discussions of research sources I use as background information in preparing writing assignments. These resources could be valuable to you as well in researching medical topics!

pmi logo

How revolutionary is personalized medicine?

The federal Precision Medicine Initiative announced on January 2015 has enjoyed broad support, but there are detractors. Soon after the announcement,  Dr. Michael Joyner wrote an op-ed in the New York Times with the view that the Initiative will not deliver as promised. his opinion prompted a large number of replies both pro and con. In July 2015, Dr. Timothy Caulfield wrote in a British Medical Journal blog downplaying the notion that personalized medicine should be considered a “revolution” and would likely follow the same path as other so-called genetic revolutions. In May 2015, Larry Husten, a medical journalist writing in Forbes,  takes issue with the rosy predictions of Victor Dzau, president of the institute of Medicine on the future of personalized medicine.

What are we to make of these opinions? In essence, do not look to personalized medicine as a panacea for human illnesses. The initial focus of the Initiative will be on cancer, an area in which personalized treatments are already well underway. Additionally, personalized medicine is showing promise in treating minor diseases  affecting  a small number of people when the disease is due to a single genetic mutation. The personalized medicine approach may not work as well in treating major diseases such as diabetes or heart disease. These diseases are more likely to be manifested due to environmental or lifestyle factors rather than defective genes,

Reservations aside, the Precision Medicine Initiative is a very welcome development. It will identify and test new targets for diagnosis and treatment of diseases, and will advance medical research.  The funds made available for the Initiative represents a small fraction of the National Institutes of Health budget, so will not handicap other vital projects of the NIH.

References

  1. Caulfield, Timothy. “Genetics and Personalized Medicine: Where’s the Revolution?” BMJ Blogs, July 23, 2015. Caulfield-BMJ Blogs
  2. Husten, Larry. “Precision Medicine Approaches Peak Hype.” Forbes, May 6, 2015. Forbes
  3. Joyner, Michael. “Moonshot Medicine Will Let Us Down.” New York Times, Jan. 29, 2015. Joyner-NY Times

PMI Image. Credit: The White House

Personalized Medicine patient

Precision Medicine Initiative

Recognizing the growing importance and promise of personalized medicine, the federal government launched the Precision Medicine Initiative with President Obama’s State of the Union Address in 2015.

A key component of the Precision Medicine Initiative (PMI) is the creation of a national research participant group, called a cohort, of 1 million or more Americans to expand our knowledge and practice of precision medicine. What is the cohort program?

Cohorts are used in a type of medical research known as an observational study. A prospective cohort study uses defined groups of people who are followed over time to see who experiences an outcome of interest. Cohort studies are useful when experimental studies are not feasible. Cohort studies are notable in requiring large numbers of people that are studied over long periods of time, particularly for less common diseases. For this reason, the PMI Working Group determined that in order to efficiently carry out the goals of the PMI, a very large cohort will be assembled over a period of 3-4 years. Researchers will be able to identify subsets of the cohort suitable for their specialized studies without having to resort to developing their own cohorts.

The participants will volunteer to provide medical history and biological specimens that will be available to researchers studying a variety of diseases and conditions.  The cohort will represent a broad cross section of the U.S. population from diverse social, racial/ethnic, and ancestral populations living in a variety of geographies, social environments, and economic circumstances, and from all age groups and health statuses.

The information obtained from the cohort will include individual variabilities in genetic, environmental, and lifestyle factors.  This knowledge will be used to develop quantitative estimates of risk for a range of diseases by combining environmental exposures, genetic factors, and gene-environment interactions; identification of causes of individual variation in efficacy and safety of commonly used therapeutics; discovery of biomarkers that identify people with increased or decreased risk of developing common diseases, as well as other medical advances.

References

  1.  The Precision Medicine Initiative Cohort Program

National Institutes of Health

PMI Cohort Program

2. The Precision Medicine Initiative Cohort Program –

Building a Research Foundation for 21st Century Medicine

Precision Medicine Initiative (PMI) Working Group Report to the Advisory Committee to the Director, NIH, September 17, 2015

PMI Working Group Report