Jing Yu
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Viruses for Good

Fighting cancer is tough. Everyday it gets tougher for scientists as the low hanging fruit are locked away behind competitive patents. The new paths to the potential cures become increasingly esoteric – the old methods are no longer effective. 2016 was our year to forge new technology to reach more fertile grounds in the fight against cancer. This is the story of the development of an innovation in a strange place – the common virus.

And everyday it gets tougher as low hanging solutions disappear behind competitive patents. For our scientists, old discovery methods had lost effectiveness and new paths to cancer drugs become increasingly complex. 2016 was a year committed to forging new technology to reach more promising grounds in the fight against cancer. This is the story of an innovation that came from a strange place – the common virus.

 

A brief background of curing* cancer

#1 compare healthy vs cancerous cells

#1 compare healthy vs cancerous cells

#2 Produce molecules that target cancerous cells

#2 Produce molecules that target cancerous cells

#3 Test if molecules call kill cell in vivo (in a tube)

#3 Test if molecules call kill cell in vivo (in a tube)

* To be clear, “curing cancer” is an overstatement that assumes cancer is one disease – but this is our in house model.

 

Rising waters

At StemCentrx, we look for proteins called antigens as a way to identify and target cancer cells. By 2016, the antigens left to pursue were so complex that studying them (let alone targeting them) became prohibitively difficult. Over 40% of our methods consistently failed to mimic the antigens we were trying to target. No antigens = no antibodies, no antibodies = no cancer drugs. The water was rising, we needed to find more powerful processes to target cancer cells. 

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Higher Ground 

There was a big push in the Research&Development team to explore alternative methods to mimic difficult antigens and recoup our lost cancer targets. Alternative methods ranging from cell based antigen presentation to DNA immunization were proposed all with mixed results.

At the cell & virus engineering department, our lead realized the potential in the viruses we routinely produced to mimic complex antigens. Viruses are natural experts in mimicking antigens from their host cells. Through some clever biological manipulation, we could leverage this expertise to force viruses to pull complex cancer antigens onto its surface and do our work for us. 

Antigens (in red) pulled onto the surface of a virus as it emerges from a host cell.

Antigens (in red) pulled onto the surface of a virus as it emerges from a host cell.

A Viral Solution

The new platform we developed was called the Lentiviral Antigen Delivery System (or LADS for short). LADS hacks viral biology and forces the LAD to display cancer targets. This process has the potential to unlock countless difficult targets StemCentrx would otherwise have lost. 

LADS also presented unique advantages (and disadvantages) over alternative methods of cDNA and cell based – best of all it repurposed an already existing process and generated the best overall results. 

Best All Around Contender  — There are almost never perfect solutions in biology, but LADS and viruses could get us as close as possible

Best All Around Contender — There are almost never perfect solutions in biology, but LADS and viruses could get us as close as possible

 Convincing the others

Though designing and producing viruses was our teams bread and butter, using LADS to display antigens and produce antibodies would make serious changes in the downstream pipeline. Leadership needed very convincing evidence before giving the green light to implement the technology company wide. 

The science of how we did this...

Our solution was novel. Viruses had not been examined like this at StemCentrx, among other reasons because viruses are very difficult to measure with standard research tools. I set on a path of hacking our available methods to study the viral particles we made. I developed a new flow cytometer assay and mined empirical data from our prototype viruses resulting in credible evidence that our LADS system worked and exceeded any of our current in house antigen technologies. 

 

Results

September 2015, LADS proof of concept experimental data was presented at our annual science meeting

September 2015, LADS proof of concept experimental data was presented at our annual science meeting

  • Successful proof-of-concept experiment presented at All-Hands Science Meeting 2015

  • Approved for additional funding to continue research  

  • Established dedicated LADS team to improve technology

  • Increased production 10% and climbing

  • Approved for 4 trial production runs, 3 of which returned effective antibodies

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Where we are today...

Science is never satisfied with one (or three) successful data points. Additional experimentation needs to be submitted to reinforce the pitch that LADS is a viable option to target difficult cancer cells.

Currently, an interdisciplinary team has been formed to perform diagnostic and characterization experiments on LADS. Together we have the means to validate LADS further as an antigen delivery system and hope to establish LADS as a powerful tool routinely used in cancer targeting.

Since the first few pilot experiments, LADS 2.0 has been an additional effort to clean up the particle. We are currently working to produce "naked" LADS that have as much irrelevant antigen removed as possible, this way the particle is 100% dedicated to mimicking cancer targets.