Everybody knows that animal models aren't really the best way to study human response to therapeutic treatment. So why do pharmaceutical companies rely on them? The answer, if you ask William Warren, is that they simply don't have a choice.
Warren is CEO and founder of VaxDesign, a company based on technology funded by DARPA that's aiming to design artificial human immune systems to bring more accurate, less expensive testing to the vaccine world.
"Drug companies would have you believe that you're a mouse," Warren says. "We're using surrogate cells and tissues that actually mimic a human immune response."
The artificial immune system technology starts with a basic microtiter plate, and the concept is that each well represents an actual human immune system. The VaxDesign scientists load each well with a layer of collagen, grow an endothelial layer on top of that, and then add blood cells from a particular donor to a single well. "In that construct we actually mimic how the antigen is processed to the antigen-presenting cells such as dendritic cells," Warren says. So far, the technology has succeeded in proof-of-principle demonstrations, he adds.
The company has built two constructs: one surrogate for lymph nodes, and another for skin. "It's not about a morphological equivalent, but a functional equivalent," says Warren, pointing out that while it's virtually impossible to make something that looks exactly like a skin or lymph system, it's a far more tractable problem to design a construct that behaves like one. "We're trying to make surrogate human constructs that mimic normal human immunophysiology."
VaxDesign, now based in Orlando, got its start in Oklahoma as a spinoff of a former DARPA-funded company. Warren says the foundations for the artificial immune system idea began when he and his colleagues began to investigate the drug development process, specifically looking for where the bottlenecks occurred. Animal models are expensive, time-consuming, and have proven to be poor predictors in many ways for human immune response.
As the company has gotten up and running, one vote of confidence came in the form of a collaboration with The Institute for Genomic Research. Eric Eisenstadt, vice president of research for TIGR and a former colleague of Warren's from their DARPA days, says, "It's just a spectacular idea to take the human immune system and convert it to a tissue culture device." He realized that with TIGR's expertise in viral genomes, for example, there was a good opportunity to team up with the VaxDesign crew for high-throughput testing of possible vaccines. "We're really excited about exploring how we might couple our functional genomics output to a system that looks as if it could rapidly screen antigen candidates to select what some of the best human vaccine candidates might be," Eisenstadt says.
In addition to the TIGR collaboration, Warren is working to get VaxDesign in partnerships with big pharma as well. "We are setting ourselves up to do a lot of high-throughput testing," he says, anticipating that scientists will come to his company with vaccine candidates and use the artificial immune system as a screening tool.
"It's a very, very different way of thinking about how to test vaccines and drugs than what is done right now," Warren says. While he knows that the success of his system won't completely obviate the use of animal models, he believes that it could significantly reduce the reliance on them. "We really need to come up with a better model that's highly ethical," he says.