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