Oncolytic viruses have long held promise for cancer treatment, but their first generation hasn’t quite delivered. Armed with new tools and technology—including 3D printing—Humane Genomics is part of a wave of companies working on oncolytic viruses 2.0.
The only FDA-approved oncolytic virus is Amgen’s Imlygic, which scored a nod in 2015 for the treatment of melanoma. Based on a herpes virus, the treatment is injected into tumors, where it replicates and produces GM-CSF, a protein that stimulates the immune response.
However, Imlygic doesn’t work in metastatic disease, and cancer-killing viruses as a whole face other barriers. A major hurdle is delivery: The viruses must be injected directly into tumors, because the immune system may catch and destroy them before they reach cancer cells if they are given intravenously. Another challenge is efficacy. The treatments don’t seem to work well on their own, and multiple companies are pursuing combinations, such as with checkpoint inhibitors and other immunotherapies.
New York-based Humane Genomics is building a platform that can design cancer-killing viruses from scratch as well as produce them and test them more quickly and cheaply than other methods.
“We can 3D print or synthesize DNA based on a computer file,” said Humane Genomics CEO Peter Weijmarshausen. “We take a file that contains A, G, C and T in the right order and feed it into a machine that produces DNA fragments,” he added, referring to the nucleotide bases or letters that are the building blocks of DNA.
Humane Genomics aims to develop viruses that not only target cancer cells while sparing healthy ones but that can also carry drugs to boost the virus’s effects or dial up the immune response against the tumor.
Weijmarshausen founded Humane Genomics with Andrew Hessel and Chad Moles, the company’s chief science officer, who focused on synthetic virology during his graduate study in biotechnology. The company picked up $125,000 in seed funding from Y Combinator this year and stands to raise more after pitching its work to investors at the startup accelerator’s Demo Day next week.
“It turns out to make a virus that is really good at identifying cancer cells and killing them requires quite a bit of engineering,” Weijmarshausen said. “It’s not that we didn’t know how to do it, but until quite recently, science lacked the tools to do it well.”
Synthetic biology, the science of redesigning organisms such as viruses for useful purposes, is just one part of the equation. The rising availability and decreasing costs of genome sequencing is the other.
Sequencing has helped drug developers understand how cancer cells are different from healthy cells and led to the creation of drugs that zero in on cancer-driving genes.
“The same is true for viruses,” Weijmarshausen said. With sequencing, scientists have learned how viruses found in nature work and can use that understanding to build synthetic viruses to fight cancer.
"We can make a new virus in about a week, and it costs a few hundred dollars,” Weijmarshausen said. In contrast, using CRISPR-based gene editing to modify a naturally occurring virus could take many more weeks and thousands of dollars, he added.
“As a result, we can take some wild gambles … This platform is completely synthetic. We are not making edits, but writing viruses from scratch, which allows us to test concepts that are going to be difficult otherwise,” Weijmarshausen said.
Instead of modifying natural viruses like herpes virus or vesicular stomatitis virus to fight cancer—and putting up with potential trade-offs or side effects—Human Genomics is cherry-picking the most desirable qualities found in natural viruses and using them to build synthetic viruses.
The company is developing its first programs for the treatment of bone cancer, liver cancer, small-cell lung cancer and a form of brain cancer called glioblastoma. It’s starting with these cancers because they’re on the rarer side and they don’t have great treatments, Weijmarshausen said.
In the near term, Humane Genomics will work on experiments to show its viruses work in mice. It is also on the hunt for partners among institutions that treat patients with the cancer types it’s interested in.
Further down the line, Weijmarshausen sees synthetic oncolytic viruses as personalized treatments to be deployed alongside routine blood testing for the earliest signs of cancer.
“Based on that detection in the blood, we’ll already know how to engineer a virus that can take care of that kind of cancer. We make it, or have it on the shelf, and you get a shot,” he said. “You may have a bit of a flu for a few days, but without you noticing you had one form of cancer or another, the virus will have killed it."