“Inverse Vaccine” to Treat Type 1 Diabetes Passes Phase I Clinical Trial

In people with type 1 diabetes (T1D), the immune system destroys the insulin-producing cells in the pancreas, leading to high blood glucose levels, which are deadly if left untreated. All people with type 1 diabetes rely on insulin injections or infusions to regulate their blood glucose levels. Individual insulin requirements are affected by many factors and tailoring the dosing regimen around the clock requires a lot of mental effort, with many patients finding it difficult to consistently achieve their target ranges.

The search for better clinical approaches for type 1 diabetes is ongoing, with many labs around the world focusing on better treatments and the ever-elusive “diabetes cure”. Most recently, researchers at the City of Hope described the first-ever human phase I clinical trial of a “inverse vaccine” to treat type 1 diabetes patients.

We previously reported on this novel potential treatment approach when it was still in its pre-clinical stages at the ADA Scientific Sessions last June. Now, we have reconnected with the lead researcher, Dr. Bart Roep, Ph.D., the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes at City of Hope and director of The Wanek Family Project for Type 1 Diabetes, to learn about the outcomes of the first-ever human trial.

What Is an “Inverse Vaccine”?

When we think of a vaccine in a traditional sense, we are usually referring to the stimulation of the immune system to develop an immunity and prevent illness from a particular microbe. An “inverse vaccine”, on the other hand, is designed to stop a specific immune response (e.g., the unwanted autoimmune response that destroys beta cells in patients with type 1 diabetes).

How Does the Treatment Work?

This treatment aims to retrain the patient’s immune system to self-tolerate the insulin-producing beta cells in the pancreas. First, specific immune cells (called dendritic cells, DCs) are collected from the patient’s blood and are specifically treated, in particular, with pro-insulin peptide and vitamin D. When the stimulated cells are injected back into the patients, in a series of “vaccinations”, they can elicit a specific subset of the patient’s T cells (regulatory T cells, or Tregs), which should, in turn, act to regulate the unwanted autoimmune response seen in type 1 diabetes.

Dr. Roep explained more:

“We want to negotiate with the immune system rather than bombard it into submission, because the latter may affect your chances of fighting off cancer and infections, including coronavirus.”

First Clinical Trial Results Show Promise

The novel vaccine was recently tested to assess safety and tolerability in nine patients with type 1 diabetes of long duration (at baseline, only three patients had detectable C-peptide levels, indicating some degree of insulin production). The results of the study were just published last week.

The treatment “passed the test” with respect to serious adverse events. The researchers describe that,

“Most importantly, there were no signs of systemic immune suppression, no induction of allergy to insulin, no interference with insulin therapy, and no accelerated loss in beta-cell function in patients with the remaining C-peptide. In conclusion, generation and intradermal administration of [the treatment] appears feasible and safe.”

Clinicians monitored various other health parameters throughout the trial, including glycemic management, which remained stable for all participants. Notably, Dr. Roep stated that,

“With regard to the unexpected clinical benefits: while we told the participating patients that it was a safety and feasibility trial, they have all-time low HbA1c years after our therapy (long after the trial ended) and on average, 13 years after their diagnosis. This is bizarre, and could point to beta-cell regeneration (perhaps once you stop the immune attack) or possibly waking up hibernating beta cells that came out of hiding after the immune system got back in check. Speculation, of course, but tantalizing observation nonetheless, in the preferred direction.”

Why were patients with long-standing diabetes selected for this initial investigation? Dr. Roep explained:

“There are two reasons why we involved patients with long-term disease.

First, to build-in extra safety precautions in this first in-human trial, we selected patients with long-term disease whose condition is less likely to worsen. After all, we injected a vaccine built on their pancreatic islets, so in theory, this could aggravate islet autoimmunity.

The other reason is a frustration that I share with my stakeholders, the diabetes patients: all efforts to intervene in the disease are biased toward a short period after diagnosis. We just learned that most patients keep beta cells for most of their lives, so it is worth protecting those beta cells and serving patients with longstanding T1D at the same time. Our novel strategy is also perfectly suited to do so: perhaps it is even smarter to negotiate with the immune system once the medical emergency is over and remaining beta cells (and the immune system) get some rest. All other strategies so far bombarded the immune system into submission; this big hammer is probably better justified early on.”

You can read even more about the study, including the patient selection process and the specific treatment protocol here.

What’s Next?

Based on the success of the phase I trial that evaluated the safety and tolerability, the research group expect to conduct more human testing:

“Our results warrant subsequent clinical testing in patients with a shorter diagnosis of type 1 diabetes and with preserved C-peptide production, to assess whether this novel immune intervention strategy is able to delay or halt progressive loss of beta-cell function. Further testing would tell whether [the treatment] protects beta cells from autoimmune destruction and can act as curative therapy for type 1 diabetes.”

Dr.  Roep and colleagues are optimistic about the future:

“Our research brings us one step closer to finding a vaccine against type 1 diabetes, an ambitious quest at City of Hope, and the hope of many patients with this disease.”

Of course, there is a long road ahead before we can know for sure whether this type of therapy will be truly effective. Moreover, the way that type 1 diabetes develops differs between patients, and it is likely that immunotherapies will have to be tailored to different patient subsets, as we previously discussed with Dr. Roep.

Nevertheless, such a tailored approach constitutes a previously unexplored form of treatment for type 1 diabetes patients, which could lead to effective therapies, and perhaps even a cure. We will continue to follow this research and provide updates as more research is conducted.

Read the official press release about this clinical trial from the City of Hope here.

Source: diabetesdaily.com

Are People with Diabetes Immunocompromised?

What does it mean to be immunocompromised?

Simply put, the term “immunocompromised” means that the person’s immune system is not functioning properly to fight off infections. This could be due to a number of reasons, including underlying health conditions, or specific medications that the person is taking.

For example, patients who are HIV-positive are considered immunocompromised. This is because HIV invades the T cells (a type of white blood cell), which are a major component of our immune system. When functioning normally, T cells help to effectively clear various infections. Because HIV affects the T cells, the immune system of these patients may not respond as effectively, and they may struggle with complications from infections that most healthy people would easily recover from.

Similarly, some classes of medications can directly inhibit immune system responses. For instance, patients who are taking anti-rejection medications following an organ or tissue transplant are considered immunocompromised. This is also the case for patients who take immunosuppressive agents for other reasons, including for the treatment of certain autoimmune conditions and cancers.

Also, because immune system function is underdeveloped in very young children and declining in the very elderly, one may consider that the very young and the very old might be considered immunocompromised to a degree (because the immune system is not functioning quite as efficiently as it does in a healthy adult).

So, what about diabetes? Could diabetes, on its own, affect our immune system function to such a degree that would be considered “immunocompromised”? Are people with diabetes, by definition of just having the condition, immunocompromised?

It is known that high blood glucose levels can negatively affect immune system function, likely doing so through several mechanisms. High blood glucose levels are linked to negative clinical outcomes in the context of infections. The importance of maintaining optimal blood glucose management, and especially during infection and in the hospital setting, has been described in the scientific literature.

It is also well-established that patients with diabetes who achieve the recommended A1c levels have a markedly lowered risk for developing infections or complications from infections as compared to those with higher A1cs. You can read more about the connection between blood glucose levels and health complications here.

One expert commentary published in the Canadian Medical Association Journal explains,

“The evidence indicates that an immunocompromised state occurs only in the context of poor glycemic control with severe complications such as diabetic ketoacidosis or in adults with vasculopathy and peripheral neuropathy.”

There is some debate concerning the pathophysiology of both type 1 and type 2 diabetes as related to aberrant inflammatory responses and what this could mean for responses to certain infections. However, this is a complex and multifactorial topic, of which much remains to be elucidated at this time, and we cannot generalize based on theoretical and/or poorly characterized physiological processes in this patient population.

What is well-established, is that for patients who are able to maintain optimal glycemic management, and in the absence of other factors (such as related complications, a medication that may suppress immune system function), diabetes, on its own, does not make the patient automatically immunocompromised. However, for patients who frequently experience very high blood glucose levels and certain associated complications, immune system function can be negatively affected. This subset of patients might be considered “immunocompromised” due to the frequency and severity of hyperglycemia as compared to those with more optimal glycemic management and/or other complicating factors.

Also, it’s important to remember that when talking about an entire population of people with diabetes, on average, these patients are more likely to be immunocompromised. In addition to (generally) having higher than normal blood glucose levels for a considerable proportion of time, many people with diabetes are more likely to also have other health conditions that may negatively affect their immune system function. One example, in particular for patients with type 2 diabetes, is obesity, which is known to negatively impact immune function.

In summary, to accurately determine whether a patient with diabetes is “immunocompromised”, we must consider their overall health, including other health conditions, the medications that they use, as well as their age and glycemic management. Simply having diabetes does not, on its own, necessarily mean that the patient is immunocompromised, although as a group, this patient population is more likely to have immune system function issues.

Source: diabetesdaily.com

Keeping Your Immune System Healthy

This content originally appeared on Beyond Type 1. Republished with permission.

By Mariana Gomez and T’ara Smith

Perhaps you’ve read about boosting your immune system to protect you from infections and other illnesses, including the Coronavirus. But, there aren’t any magic foods, supplements, or one-size-fits-all solutions to boosting your immune system because it’s a complex network of cells, organs, tissues, and proteins. Still, healthy living provides its benefits, including keeping our immune systems strong, and research is being conducted to study the effects of nutrition, exercise, mental health, and others on our immune response.

How Diabetes Impacts Your Immune System

Type 1 diabetes is an autoimmune disease. There is not enough evidence to identify the cause but we know that our immune system insulin-producing cells are destroyed. We now know that people with type 1 diabetes are more likely to have a co-occurring autoimmune disorder. The reason that co-occurring autoimmune disorders are so common isn’t yet known. We also know that hyperglycemia can affect our immune system’s response so it would represent a barrier for recovery and fighting virus and bacteria. This does not happen only in type 1 diabetes (T1D) but other types of diabetes as well.

People with type 2 diabetes should be aware of the impact the disease has on their immune system as well. Hyperglycemia in diabetes is a probable cause of the disruption of how the immune system functions. Humans also produce “natural killer” cells that are critical to human immunity. A study showed people with type 2 diabetes have lower counts of these cells compared to those without diabetes and with prediabetes. This makes it harder to defend the body against viruses, diseases, and diabetes-related complications.

Overall, people with diabetes are more susceptible to common infections such as the flu and pneumonia. To protect your immune system, stay up-to-date on your doctor’s visits, get vaccinated against the flu, and get screened for complications.

Essential Nutrients for a Strong Immune System

Another way you can protect your immune system is through nutrition. With a healthy diet, food can help protect you against illnesses and help improve recovery. Different foods contain different quantities and types of nutrients and micronutrients. Therefore it is important to include a variety of food groups in your diet. Vitamins A, B6, C, E, magnesium, and zinc play important roles in our immune function.

How Vitamins + Minerals Help Your Immune System

Vitamins and minerals are known as essential micronutrients. Even though they are needed for our health, our bodies can’t make them on our own or enough of essential micronutrients, therefore, they must be obtained through food. There are nearly 30 vitamins and minerals the human body can’t make on its own. A healthy diet will include different groups of foods that contain some of these nutrients.

Micronutrient malnutrition results in a lack of vitamins and trace minerals that can affect the response of our immune system to fight different health conditions. The NIH lists the recommended dietary allowances (RDA) for vitamins and minerals. While this provides general guidelines for different age groups, please talk to a nutritionist or your doctor about recommended intakes for you.

Vitamin A is an anti-inflammation vitamin that helps develop and regulate the immune system and protect against infections. This Vitamin can be found in sweet potatoes, carrots, broccoli, spinach, red bell peppers, apricots, eggs, and milk. While vitamin A is important, it is possible to consume too much of it. High intake of vitamin A from supplements and some medications can cause headaches, dizziness, coma, and death. According to the NIH, pregnant women shouldn’t consume high doses of vitamin A supplements.

Vitamin B6 helps improve immune response to the increase in the production of antibodies, a protective protein produced by the immune system to fight antigens in the body. Vitamin B6 is found in a variety of foods. Food sources of vitamin B6 include pork, fish, poultry, bread, eggs, cottage cheese, tofu, and wholegrain foods such as oatmeal and brown rice. Getting too much vitamin B6 from food is rare. However, from supplements, long-term use for a year or more can lead to nerve damage.

Vitamin C also known as ascorbic acid, helps your immune system by fighting free radicals that cause cancer and other diseases. It’s a popular nutrient to fight or treat the common cold. While focusing on vitamin C consumption may not prevent you from getting sick, it could decrease the length and severity of cold symptoms. It also helps by stimulating the formation of antibodies. This vitamin can be found in oranges, grapefruit, tangerines, red bell pepper, papaya, strawberries, tomato juice, among others. Too much vitamin C can cause diarrhea, nausea, and stomach cramps.

Vitamin E works as an antioxidant, which protects the cells from damage by free radicals and helps the body fight infections. This vitamin can be found in sunflower seeds, almonds, vegetable oils, hazelnuts, and spinach and other green leafy vegetables. There isn’t a risk of consuming too much vitamin E from foods. Precautions should be taken when taking supplements, which could interfere with other treatments such as chemotherapy or radiation therapy.

Magnesium is a nutrient that our body needs to regulate the function and work of our muscles and the nervous system. It is involved in the process of forming protein, bone mass and genetic material. It is found in legumes, nuts, seeds, whole grains, green leafy vegetables, milk, yogurt among others.

Zinc is found in cells throughout the body. It helps the immune system fight bacteria and viruses and is needed to produce proteins and DNA. During pregnancy, infancy, and childhood, the body requires zinc to grow. Zinc can be found in oysters, red meat, poultry, crab, lobster, cereals, beans, nuts, whole grains, and dairy products.

Drinks That Help Your Immune System

You can find or create your own drinks to help your immune system. Some beverages you may want to try at home that are high in important immune-friendly vitamins are:

*Juices may be high in carbs and sugar, so if you can, opt for unsweetened teas like green/chamomile teas, or whole fruits.”

Alcoholic beverages are generally fine to consume in moderation. Drinking too much alcohol can lead to a weaker immune system. Heavy drinkers are more likely to get pneumonia and drinking too much alcohol at once can slow your body’s ability to ward off infections.

Should You Use Supplements to Help Your Immune System?

Supplements are used in cases where diet is not able to sufficiently provide micronutrients. While supplements aren’t meant to replace a balanced diet, they’re used to help people with other health conditions and may be prone to nutrient deficiencies. Many vitamin and mineral supplements can be purchased over the counter. But, check with your physician or a registered dietitian nutritionist to see if you actually need them. If you’re taking other medications, talk to your doctor on how vitamin and mineral supplements can interfere with those drugs.

Other Things You Can Do to Stay Healthy

A healthy diet is definitely a big part of remaining healthy. Other things you can do on a regular basis to maintain your health is to practice good hygiene (i.e. washing your hands), see your healthcare provider routinely, keeping an emergency medical plan and your emergency contacts updated. Also, prioritize physical activity and refrain from smoking. From a mental and emotional health perspective, practice stress-relieving techniques and know the signs of diabetes burnout.

Source: diabetesdaily.com

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