#conjugates

Brilliant Violet Antibody Conjugates

Antibody drug conjugates (ADCs) are therapeutic agent which combines the targeting capability of monoclonal antibody (mAbs) and of cytotoxic agent which targets and kills cancer cell without affecting healthy cell. Based on type, the ADC can be classified into Kadcyla and Adcetris. These drugs can be used in specialized cancer centers, hospitals, biotechnology companies, academic research institutes, biopharmaceutical companies, and others. Different technologies involved in the development of ADC include ImmunoGen, Seattle Genetics, and Immunomedics.

Rise in Breast Cancers to Boost Demand

Based on mechanism of action, the ADCs can be bifurcated into immunoglobulin G (IgG1) antibodies and human epidermal growth factor receptor 2 (HER2) antibodies. IgG is an antibody containing four peptide chains. It controls the infection of tissues by binding to pathogens such as fungi, bacteria, virus, etc. These antibodies play crucial role in antibody dependent cell-mediated cytotoxicity (ADCC) and intracellular antibody-mediated proteolysis. The IgG1 antibodies segment is expected to generate demand in the coming years due to its utilization in the development of drugs and immunotherapy.

For instance, on 26 January 2018, Merus N.V. declared the news that the first patient has been dosed in a Phase 2 clinical trial for evaluating MCLA-128, an IgG antibody. This trial is intended for two metastatic breast cancer (MBC) populations, hormone receptor positive 2/HER2-low MBC patients, and HER2-positive MBC patients. It blocks the HER3 signaling pathway using dock and block mechanism.

Market Overview

The antibody drug conjugates (ADCs) market is expected to show rapid growth by 2023. Growing geriatric population, advances in medical technology, strong drugs pipeline, and demand for cost-effective treatment for cancer can propel the market during the forecast period (2018 to 2023). However, high costs involved in the drug development may restrict market growth to an extent.

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People in my lab (Mark and Jay, I'm talking about you guys) have finally found my blog and were wondering why I haven't posted in a while. Well the only excuse I could come up with was to blame it on my controlled addiction to twitter. Typing out <150 characters is a lot easier than long(ish) blog posts. The wider (sciencier) audience makes it all more the more attractive. Then again, I am not going to completely give up on this blog yet. So here it is -

Recently, I had the pleasure to listen to John Lambert, CSO of Immunogen, a biotech leader in Antibody-drug conjugate (ADC) development. They already have a breast cancer, ADC drug (Kadcyla) in the market with the help of Genentech. I am going to let the following video explain the basic concept of why we want drugs conjugated to antibodies -

I wanted to point out a couple of not-so-eye-popping yet crucial factors that were not really clear to me, someone not working in this field.

Simple logic suggests that localized delivery of a cytotoxic drug to cancerous cells/tumors by conjugating it to a target-specific antibody (that may or may not already have intrinsic cytotoxic effect) is the pinnacle of drug therapy. But adding a drug molecule into the equation brings us face-to-face with a whole other monster - Pharmacokinetics!

Typical antibodies have the advantage of being made up of aminoacids just like any other protein in our body and their metabolism is therefore not a major concern during drug development. ADCs, on the other hand, have a cytotoxic drug that gets metabolized into products which requires developers to extensively study their toxicity and their kinetics.

You might wonder, Why is this so important? If these molecules are at the tumor site, and if the metabolic products are toxic, shouldn't they be all the more effective in killing the cancerous cells?

Well, the important thing to keep in mind is that almost all anti-cancer antibodies target specific proteins (HER2, EGFR, etc.) that are highly expressed on the cell-surface of cancer cells. But, these proteins are also expressed (in lower concentrations) on normal cells. Although these ADCs are considered to be "magic bullets", when administered, they move throughout the body (in our bloodstream), attach to both normal and cancer (predominantly) cells and hence can get metabolized throughout the body. 

But it is not all gloom and doom for ADC therapies. Due to the targeting effect of the antibodies, the concentration of drug molecules required to have a viable effect is much lower than typical radiation/chemo therapies using the drug by itself. Therefore, they have a similar toxicity profile to that of the chemotoxic drugs, but generally better tolerated by patients.