The Story Behind Tumor Paint

Project Violet

The Story Behind Tumor Paint

Dr. Jim Olson recalls the early days of its development

Imagine what it felt like when, an hour after we injected a molecule we called “Tumor Paint” into the tail of a mouse that had a brain tumor, the tumor was glowing brightly and the rest of the mouse was not.

Lung tissue comparison

The image on the left is a piece of lung tissue that contains a tumor viewed under normal white light. The right image shows the same piece of tissue after Tumor Paint has been applied. Here it's viewed under infrared light. Areas that are more red and yellow show a concentration of the paint, which means they are more likely to be cancerous.

Courtesy of Julie Novak/Blaze Bioscience

Two grown men.
Wearing white lab coats.
Dancing in the halls of Fred Hutch.

By linking a peptide (mini-protein) from the Israeli deathstalker scorpion to a “molecular flashlight,” we created the first Tumor Paint and in 2007 reported our findings from non-clinical studies that this molecule clearly distinguished cancer from normal tissue. We have since initiated human clinical trials of BLZ-100, the clinical candidate that emerged from those early studies.

When we first proposed Tumor Paint in grant applications, peer scientists said our ideas were “too speculative,” “overly ambitious” and “may not work.” The first six grants I wrote for Tumor Paint were not funded for these reasons.

But rather than shrink the science to meet the budget, we raised the funds to fuel our research. The families of pediatric brain tumor patients in our practice held fundraiser after fundraiser and, ultimately raised more than $8 million to support Tumor Paint and other innovative research. Where there’s a will, there’s a way.

In 2011, we created Blaze Bioscience to advance Tumor Paint molecules to human clinical trials and hopefully FDA approval. The Blaze team has exceeded expectations as they have advanced BLZ-100 to human clinical trials on time and within budget.

The optide platform – human ingenuity optimizing nature’s best

Plants and animals need drugs to survive every day and they can’t run to the drugstore to get them: they must make effective drugs or die.

Twenty-three years ago, some very smart scientists recognized that a particular type of mini-protein (“peptide”) drug made by scorpions, spiders, cone snails and some plants would be a perfect starting point for new drugs for human diseases.

Tumor paint is an optimized version of one of these peptides and was therefore our first optimized peptide.

Taking Tumor Paint to human clinical trials required our team to overcome several daunting challenges. For example, we started with a peptide that only lasted a few minutes in the bloodstream before being eliminated in the urine. We worked successfully to figure out how to optimize the peptide to make it last many hours.

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We realized that such lessons learned in developing Tumor Paint could help us develop optide drug candidates for other diseases — but we were immediately faced with new hurdles. The biggest challenge was finding a way to make thousands of drug candidates rather than just a few. During the peak of our activity on Tumor Paint, we could only make a dozen or so drug candidates a year because each had to be made by hand and tested extensively to see if the "molecular knot" was tied properly.

Why is it important to be able to make thousands of candidates rather than dozens? Think of a particular disease as a lock and the drug that will cure it as a key. The chance of success is much greater if we start with thousands of keys that varied greatly in size and shape. Once we find a few that are at least close, we can make changes until one of them finally opens the lock.

With a turbo-charged effort over the past few years, our team has overcome major hurdles that previously prevented scientists from making thousands of knotted peptide drug candidates. In the beginning, we made about 12 optide candidates in one year. Now we can make up to 10,000 in three weeks!

As described in the following video, the optide platform we are developing offers one-of-a-kind hope for those with rare diseases — diseases that are unlikely to receive attention from pharmaceutical companies. Our efficiency is so great that we believe it might be possible to get 50 optide drug candidates into human clinical trials for about the same cost that it takes to get one drug approved by the FDA through traditional pharmaceutical companies.

We are the only group of scientists in the world that can create thousands of optide drug candidates. We wish to share these candidates with other scientists to collaborate on diseases that are currently considered incurable. Twenty years from now, we want to look back and know that we did everything possible we could. We rely on you, through Project Violet, to financially support our scientists as we focus our ingenuity, hard work and experience on the most challenging diseases that face children and adults.

 

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