New Cancer Treatment Techniques: Antibody Drug Conjugate & Peptide Drug Conjugations

The efforts to find a cure for cancers have been ongoing since long time ago. Yet, no effective methods or drugs are discovered by now. Scientists and doctors never stop their steps along this journey with the pains and sufferings of cancer patients echoing in their minds. But with the advance in science and technology, new emerging techniques do make their presence and share their role in the battles against various cancers.

Among them bioconjugation is worthy of mentioning here. As its name suggests, bioconjugation is basically a technique used to form a stable covalent link between at least two different molecular parts of biological origin. Through this technique new chemicals can be made or some biomolecules are able to take on certain personalized new looks. Despite its limitations in specificity, stability and bioavailability, bioconjugation is widely used in biomedical researches given its great potential in cancer treatment.

Of course, when talking about new cancer treatment techniques, we cannot miss antibody drug conjugates and peptide drug conjugates. With application of them, new drugs to cure cancer may be discovered.

Antibody Drug Conjugates (ADCs)

ADCs are virtually complex molecules that are composed of an antibody linked to a biologically active cytotoxic payload or drug. Ever since the advent of ADC technique, it has gained remarkable attention and gradually revolutionize the field of cancer chemotherapy.

What makes it stand out among all breakthroughs in the biopharmaceutical industry is ADCs intend to target and kill exclusively the cancer cells and thus spares healthy cells. This differentiates itself from the conventional treatments which will also damage healthy tissues during dose escalation.

Peptide Drug Conjugations

Peptides are considered as an important type of molecules to be derived using the bioconjugation technique. Peptide drug conjugate holds a promising stance in targeted cancer therapy as it enables the delivery of therapeutic agents by providing distinct advantage of improving therapeutic potential of drugs. Through synthesis and modification of different categories of peptides, this technique will exert considerable impact on academic research, clinical diagnostics, the production of therapeutics and more.

Research is ongoing for the development of new drug delivery systems for targeted drug delivery. Peptides derived from sequence of cell surface proteins have shown potent binding affinity to the target cell surface receptors. Equipping peptides-drug conjugates with target cell specific ligands like EGF and RGD peptides can provide a solution for selective and targeted delivery.

With the discovery and application of such new techniques, cancer may be cured in the near future.

Finding the Right Partners Is Key to Success of Monoclonal Antibody Production

Biopharmaceutical as a growing industry is not merely conjecture at this point. The BioProcess Technology Consultants in a 2011 report said that the total revenues among biopharma companies surpassed $100 billion in 2010. But the industry is far from peaking as companies are expected to increase their spending to $200 billion by 2015. But there’s a wide gap between the demand for cell line development and the ability of global pharma companies to build new capacities to fill that gaping hole. This issue won’t affect the huge multinationals more than the smaller companies that can no more afford to invest in these facilities nor pick the scraps left behind by the multinationals.

The rise of CMOs

This is the reason why the number of contract manufacturing organizations is growing very rapidly because they enable smaller biopharma companies to compete. Of course huge companies are also outsourcing some of their production needs not only to cut costs but also to ensure that new product lines are religiously being rolled out. In fact, biologics represent more than 3 in 10 drugs in the development stage in the world. Companies have found the value of outsourcing their requirements for cell line development, biosimilars or biobetters.

Expiring patents

It’s easy to think that the market is already saturated with CMOs, but you would be wrong. Between 2011 and 2018, for example, blockbuster biologics (or those belonging to the top 30 biologics) worth $30 billion in Europe alone are scheduled to lose their patent protection. That means a free-for-all frenzy to develop similar products that may be cheaper and better. Whether you can afford to

Working with a pro

There’s an unjust apprehension regarding biosimilars, and maybe you can include there the Biobetters, but this is typically driven by the type of research and development methods being employed as well as the facilities used to manufacture those products.

Therefore it’s paramount that you work with a professional with the track record and the knowhow to deliver your requirements on time and on competitive rates. In a cutthroat industry, it’s important to gain whatever edge you can get and selling cheaper medicine is always a nice marketing come-on. To think about partnering with CMOs for radiolabeled antibody products or cell line development in order to cut costs is a shallow way of looking at it. More than the savings, it’s one way to make sure that whatever drug is being sold in shelves is not compromised by the biopharma company’s decision to cut some corners in safety procedures and quality ingredients.

Celiac Disease Versus Gluten Sensitivity – New Role For Genetic Testing and Fecal Antibody Testing?

Celiac disease (CD) has a prevalence of 1/100. Between 90-99% of Celiacs are HLA DQ2 and/or DQ8 positive. Every individual has two DQ serotypes. Because the molecular HLA nomenclature can be confusing DQ serotyping is a method for simplifying the results. There are four major types and 5 subtypes: HLA DQ1, DQ2, DQ3 and DQ4; DQ1 has two subtypes; DQ5 and DQ6 whereas DQ3 has three subtypes; DQ7, DQ8 and DQ9. Each individual has two copies of HLA DQ. One DQ type is inherited from each parent.

Though 35-45% of individuals of Northern European ancestry are DQ2 &/or DQ8 positive only 1% have classic CD as defined by abnormal blood tests and small intestine biopsies. Several autoimmune conditions also occur more frequently in DQ2 and DQ8 positive individuals.

There is accumulating scientific evidence that many individuals are gluten sensitive and respond to a gluten free diet though they have normal blood tests and/or normal intestinal biopsies (fail to meet strict criteria for CD). This is more commonly being referred to as non-Celiac gluten sensitivity (NCGS). Many individuals who have NCGS are relatives of confirmed Celiacs and were previously referred to as latent Celiacs. Electron microscopy and immunohistochemistry studies of individuals with normal biopsies but suspected of or at risk (1st degree relatives of Celiacs) have revealed ultrastructural abnormalities of the intestine and those who chose a gluten free diet usually responded and many who did not ultimately developed abnormal biopsies on long term follow-up. Seronegative Celiac has also been recognized, that is blood tests are negative, but the biopsy reveals classic abnormalities of Celiac and the individual responds to gluten free diet.

Testing for DQ2/DQ8 has been suggested as a way to exclude CD. That is, if you are negative for DQ2 and DQ8, then you are very unlikely to have CD. However, well documented cases of CD and Dermatitis Herpetiformis (DH) have been confirmed in DQ2 and DQ8 negative individuals. Moreover, we now have the clinical experience that other DQ patterns predispose a person to gluten sensitivity because these individuals frequently have elevated fecal antibodies to AG or tTG and respond to a gluten free diet.

Why some people develop Celiac Disease or become gluten sensitive is not well understood. Risk factors include onset of puberty, pregnancy, stress, trauma or injury, surgery, viral or bacterial infections including those of the gut, medication induced gut injury or toxicity (e.g. NSAIDs), immune suppression or autoimmune diseases, and antibiotic use resulting in altered gut flora (dysbiosis). The severity of the sensitivity is related to the DQ type, pre-existing intestinal injury, degree of exposure to gluten (how frequent and large a gluten load an individual is exposed to), and immune status. Once initiated, gluten sensitivity tends to be lifelong. True CD requires lifelong complete gluten avoidance to prevent serious complications, cancers, and early death.

Serotypes can be determined from blood or buccal mucosal cells (obtained by oral swab) from several commercial labs including Prometheus, Labcorp, Quest, The Laboratories at Bonfils, and Enterolabs. Fecal IgA anti-gliadin and IgA tissue transglutaminase antibody testing is only available in the U.S. commercially through Enterolabs. The fecal AG and tTG testing may be helpful in those with normal blood tests for Celiac and/or a normal small bowel biopsy but suspected of being gluten sensitive. Though the fecal antibody results are not widely accepted by many “Celiac experts” numerous testimonials of individuals testing positive only on fecal tests who have responded to gluten free diet can be found in support groups, web postings, personal communication from Dr. Fine and this physician’s clinical experience.

Fecal antibody testing for gliadin (AG) and tissue transglutaminase (tTG) by Enterolab in Dallas has revealed elevations in 100% of Celiacs tested and up to 60% of symptomatic individuals without Celiac disease (NCGS) even if not DQ2 or DQ8 positive. The only DQ pattern he found not associated with gluten sensitivity is DQ4/DQ4, a pattern typically found in non-Caucasians who are known to have a low prevalence of Celiac disease.

Bibliography

Abrams et.al. Seronegative celiac disease:increased prevalence with lesser degrees of villous atrophy. Dig Dis Sci 2004;49:546-550.

Alaedini A. and Green P.H.R. Narrative Review: Celiac Disease: Understanding a Complex Autoimmune Disorder. Ann Intern Med. 2005;142:289-298.

Arranz et. al. Jejunal fluid antibodies and mucosal gamma/delta IEL in latent and potential coeliac disease. Adv Exp Med Biol. 1995; 371B:1345-1348.

Dewar D. and Ciclitira P. Clinical Features and Diagnosis of Celiac Disease. Gastroenterology 2005;128:S19

Kappler et.al. Detection of secretory IgA antibodies against gliadin and human tissue transglutaminase in stool to screen for coeliac disease in children:validation study. BMJ 2006; 332:213-214

Kaukinen et.al. HLA-DQ Typing in the Diagnosis of Celiac Disease. Am J Gastroenterol. 2002;97(3):695-699.

Fine KD and Rostami K. Don’t throw the baby out with the bath water. BMJ February 13, 2006 rapid response editorial

Fine K. Early diagnosis of gluten sensitivity before the villi are gone. Transcript of presentation to Greater Louisville Celiac Support Group, June 2003.

Picarelli et.al. Antiendomysial antibody detection in fecal supernatants:in vivo proof that small bowel mucosa is the site of antiendomysial antibody production. Am J Gastroenterol. 2002 Jan;97(1):95-98

Sbartati A. et.al. Gluten sensitivity and “normal” histology: is the intestinal mucosa really normal? Dig Liver Dis 2003;35:768-773.

Sollid L. and Lie B. Celiac Disease Genetics:Current Concepts and Practical Applications. Clinical Gastroenterology and Hepatology 2005;3:843-851.

WGO-OMGE Practice Guideline Celiac Disease. World Gastroenterology News. 2005;10(2):supplement 1-8.

Thyroid Antibodies and Graves’ Disease

Many people with Graves’ Disease actually have a negative test for thyroid antibodies. So while a positive test for thyroid antibodies, along with a positive Radioactive Iodine Uptake test will confirm you have this condition, one can’t rely on the thyroid antibodies blood test alone. So while some doctors will recommend a TPO or a different blood test to detect thyroid antibodies when they suspect someone has Graves’ Disease, others won’t recommend any of these blood tests at all.

What is the purpose of receiving a blood test for thyroid antibodies? Well, normally antibodies are formed to protect the body from foreign molecules, also known as antigens. With Graves’ Disease, which is an autoimmune thyroid condition, the antibodies attack its own thyroid gland. So tests for thyroid antibodies such as the TPO can help determine the presence of these antibodies, although as mentioned above, one can’t rely on these tests alone.

As a holistic healthcare professional who was personally diagnosed with Graves’ Disease, I can tell you that while I do consider the test for thyroid antibodies to be helpful, there are other more useful tests which will actually determine the cause of this autoimmune thyroid condition. After all, while it’s nice that there are tests to confirm you have Graves’ Disease, there are other tests which can help determine the cause of this condition. Although most endocrinologists and other doctors consider Graves’ Disease to be incurable, many people have had their health restored back to normal by following a natural treatment protocol.

Other Tests Which Can Determine The Cause Of Graves’ Disease

If you are looking to determine the cause of your condition, and avoid taking anti-thyroid drugs and/or receiving radioactive iodine, then in addition to the thyroid antibodies blood test and other thyroid blood tests which can help diagnose your condition, there are a few tests that can help determine the cause of your condition:

Test #1: Adrenal Stress Index (ASI). Such a test is useful to determine the state of the adrenal glands. Although this test measures a few different hormone levels, perhaps the most important values are the cortisol levels. Cortisol has many different functions in the body, and one of the more important functions is to regulate the blood sugar levels. When someone eats poorly over a long period of time or deals frequently with chronic stress, this in turn can weaken the adrenal glands, which will affect immunity. This in turn can lead to the development of an autoimmune thyroid condition. This was a very valuable test when I was diagnosed with Graves’ Disease, as both my early and late morning cortisol levels were low, which meant I needed additional adrenal support. I use the company Diagnos-Techs for this test, as they have a great reputation and haven’t let me down so far.

Test #2: Hair Mineral Analysis. A hair mineral analysis test can also be useful, although it tells us a different “story” than an ASI. This test will tell you what is happening at the cellular level, detecting deficiencies in minerals such as sodium, potassium, magnesium, calcium, and other minerals which also can affect thyroid health. Most endocrinologists would laugh at you if you told them you wanted to obtain such a test. But done by a quality lab, a hair mineral analysis can provide some valuable information to help determine the cause of your condition. Obviously a deficiency in one or more of these minerals isn’t only related to the cause of your autoimmune thyroid disorder, as these deficiencies can lead to numerous other conditions as well.

Test #3: Hormone Panel. I also use Diagnos-Techs for this test, as this is yet another saliva-based test, and it can help determine if you have a hormonal imbalance which is causing or contributing to your autoimmune thyroid condition. It measures the hormones estrogen, progesterone, testosterone, and numerous other hormones which can be imbalanced and be causing or contributing to your condition.

It’s important to point out that it takes many years to develop Graves’ Disease. As a result, not only does it take time to develop a hormonal imbalance, adrenal fatigue, etc., but it takes time for these problems to lead to an autoimmune thyroid condition. And of course sometimes these don’t directly cause Graves’ Disease, but are instead contributing factors to this condition.

Which of these tests should you receive? It depends on numerous factors, and some holistic doctors will recommend that each of their patients receive all three of these tests initially. This isn’t necessarily a bad idea, as they all provide valuable information which can help determine the cause of Graves’ Disease. On the other hand, some holistic doctors will recommend only one or two of these tests based on the patient’s symptoms. So for example, if someone is having the symptoms of estrogen dominance, then the doctor will most likely recommend a hormone panel. If they are experiencing symptoms of adrenal fatigue, then chances are an Adrenal Stress Index will be recommended.

Using Tests To Follow Up On One’s Progress

In addition to using tests to help diagnose Graves’ Disease and determine the underlying cause of the condition, these tests can of course also be valuable in determining one’s progress when following a natural treatment protocol. When I was diagnosed with Graves’ Disease, it was a great feeling to see the thyroid blood tests which were once positive become negative again. It was equally gratifying to see the other tests normalize as well, such as the cortisol levels in the Adrenal Stress Index test.

How frequently should one use these tests as a followup procedure? There is really no exact answer to this, as I personally recommend that my patients receive follow up tests every 3 to 6 months. This pertains not only to the thyroid blood tests (TSH, free T3 & T4, thyroid antibodies, etc.), but also to the three tests I mentioned above. Some doctors will recommend that their patients receive them more frequently. Of course patient finances do play a part in this, as while I don’t see anything wrong with someone wanting to obtain these tests every 6 to 8 weeks, some patients simply can’t afford to do this.

Similarly, while I prefer that patients receive follow up tests every three months until they have normalized, some people can only afford to receive them every six months. And as long as they are improving from a symptomatic perspective, I don’t see a reason to test them too frequently. This of course isn’t to suggest that I only pay attention to the symptoms, as this definitely is not the case. However, a reduction in symptoms is a good sign that the patient is improving, and so if someone keeps on getting progressively better, then there isn’t as much of an urgency to repeat a test when compared to someone who isn’t getting good results.

On the other hand, many patients who are getting significant improvement from a symptomatic standpoint can’t wait to obtain follow up tests in order to see the improvement. I know this was the case with me, as I was excited to see the positive changes on the tests, as in my mind this really confirmed that the natural treatment methods were working. So even though I began experiencing an improvement in symptoms after only a few weeks of treatment, seeing the improvement in the follow up tests was what really got me excited about this.

Who Can’t Be Helped By Natural Treatment Methods?

While I have so far raved about the effectiveness of natural treatment methods, the truth is that not everyone with Graves’ Disease can have their health restored back to normal. However, most people can benefit from following a natural treatment protocol. After all, anti-thyroid drugs do nothing but manage the symptoms. And while this is sometimes necessary, especially when someone has a high pulse rate and/or palpitations, it is no cure for this condition. The same thing applies to radioactive iodine treatment, as while this will usually eliminate the hyperthyroid symptoms, the person will frequently become hypothyroid and will need to take thyroid hormone for the rest of their life.

Your best bet is to seek the advice of a competent natural endocrine doctor, preferably one who has a great deal of experience dealing with Graves’ Disease cases. Unfortunately there aren’t too many of these doctors out there, but there are some good holistic doctors which can recommend a protocol to help you restore your health back to normal.

In summary, thyroid antibodies can help determine whether someone has Graves’ Disease, but having this test alone isn’t enough to diagnose this condition, as well as to measure the progress of someone. Other tests need to be performed, but just remember that the tests commonly recommended by endocrinologists and other medical doctors don’t determine the actual cause of Graves’ Disease. In order to accomplish this, other tests are needed, and can be extremely valuable for anyone looking to restore their health through a natural treatment protocol.