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By Rashmi Nemade, Ph.D.

If you’ve ever built with Legos or watched someone else build with them, you know that there are hundreds of sizes of bricks, maybe thousands or even tens of thousands. Builders use small bricks to make larger masterpieces. Without different configurations of the smaller pieces, you can’t get to the larger picture – a functional larger sculpture or toy.

What are peptides?

So, too, is the way of biology. Our bodies use smaller building blocks to be functional. Everyone’s heard of protein. Yes, it’s something you eat as a part of a balanced, healthy meal. Proteins are made of peptides, which are in turn made by amino acids. Amino acids are the individual Lego brick. When you put two or more of them together, you get a peptide, and when you create something even bigger, you get a protein. Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells and are required for the structure, function, and regulation of the body's tissues and organs.Proteins, naturally, do all kinds of things in our bodies; they createhormones, antibodies, and anti-toxins – just to name a few. But just like a big Lego masterpiece is difficult to use for multiple purposes, so is a protein. A more flexible multi-use candidate is a smaller brick combination or a peptide. It’s easier for a peptide to fit into multiple places and be useful for multiple functions.

What are immuno-modulating peptides?

When a peptide therapeutically alters the immune system, it is known as an immuno-modulating peptide. For example, antibiotics are peptides that destroy the bacteria that cause illness. To us, they are therapeutic, but don’t do a whole lot to change our biology, except make us feel better. However, a peptide that alters our immune system to fight, say cancer,is animmuno-modulating peptide that steps in line with our immune systems to fight disease. In cancer, these therapies are called immuno-oncology therapies or simply immunotherapy. They reduce the need for chemotherapy and minimize dangerous side effects. There are several immuno-oncology peptides being used in cancer therapy today.[1] By using these immunotherapies, treatments have become more effective.

Finding more bricks

So, if you want to build something better, like a new Lego masterpiece, you need more bricks, maybe different bricks. The same is true with immunotherapies. We can all agree that we need more options for effective cancer treatments. How do we find more Legos? Well, I guess we could go to the store, but that doesn’t work for immunotherapy. We have to find them.

That’s where the aquatic microbiome comes into the picture – that’s our store [3]; except that all our usable pieces are mixed in with things we don’t necessarily need, so we have to sort them. In our last blog, we described the untapped potential of the microbiome and Biosortia’s technology to literally sort through and find bioactive peptides.With today’s technology, it is possible to ‘design’ peptides in the laboratory, but just putting amino acids together in combinations does not mimic the brilliance and diversity of nature, nor does it automatically impart bioactivity.

Peptide drug market

Today, over 60 peptide drugs are approved in the United States and other major markets.[2, 4] Peptides are versatile – they are highly selective for their targets, effective, and well-tolerated therapies. Thus, it stands to reason that having more bioactive peptides would offer more options. In 2015, there were approximately 140 peptide therapies being evaluated in clinical trials and over 500 therapeutic peptides in preclinical stages.[4]

Clarivate Analytics

Just a few weeks ago, Clarivate Analytics released their 2017 Year in Review for the Life Sciences. In it, they state that Oncology represents the largest activity for large Biopharma with over $30 billion in overall transactions with immuno-modulating peptides outnumbering most other therapeutic interests, save for small molecules.[5] Currently, there are approximately 250 drug molecules in active development and over 20 specific immuno-oncology therapeutic targets under investigation (Figure 1).[5] It is clear that the search for cancer immunotherapy is increasing. Keeping pace with discovery, peptide-based therapeutic products are receiving an increasing rate of approval by the US FDA. Immuno-oncology therapies could be unparalleled in their ability to treat and cure patients.

Figure 1. There are currently over 20 immuno-oncology therapeutic targets under investigation.

Back to Legos

Wouldn’t it be great if we had an unlimited supply of bricks with which to make Lego masterpieces? Better yet, what if while we are building, we could find exactly matched brick combinations that accelerated our creative process? That is exactly what nature does with peptides. In an aquatic environment, the microbiota uses it’s amino acid building bricks to make countless peptide combinations - peptide combinations that could be therapeutic, if only we could find them. Biosortia’s technology allows us to do exactly that through harvesting, mining and screening for bioactive peptide combinations. It gives the industry powerful and efficient access to the metabolites of unculturable microorganisms at 1 part/trillion yieldingapproximately 100mg for study. This is the current revolution in immuno-oncology. Wonder if we could use the same technology for sorting Legos at the Lego Store.



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