A University of Pennsylvania biotech spinout recently launched its first clinical trial of an experimental cancer treatment for hard-to-treat solid tumors.
Its approach builds upon groundbreaking work harnessing the body’s immune system to fight cancer.
Based in Philadelphia and San Francisco, the company, Dispatch Bio, launched a year ago with CAR-T pioneer and Penn researcher Carl June as a scientific co-founder and $216 million in funding from private investors.
The company aims to succeed where CAR-T, an immunotherapy that genetically modifies a patient’s immune cells to recognize and attack cancer, has struggled.
Although CAR-T has revolutionized the treatment of blood cancers, scientists have yet to replicate that success in solid tumors. By painting a target on tumors and revving up the immune system, Dispatch believes its platform could.
It dosed its first patient earlier this month.
“With one approach, we are addressing the two main challenges that we have faced over the last decade or so,” said Mauro Avanzi, the chief medical officer of Dispatch.
Success is not guaranteed. Most exploratory scientific efforts do not advance to the point where they are found safe and effective in humans. Even if the results are promising, it could take years before a potential new treatment becomes widely available.
Dispatch’s first clinical trial focuses on advanced gastrointestinal cancers, including cancers of the stomach, esophagus, and colon. The company also announced a clinical trial earlier this year in China that has not yet started dosing patients.
If the treatment turns out to be safe and effective, Dispatch hopes to expand to other solid tumor types with significant unmet need.
“As many patients as we can deliver that for, we will keep striving to do,” said Lex Johnson, Dispatch’s co-founder and chief platform officer.
‘A Trojan horse’
Solid cancers are notoriously difficult to treat with immunotherapy for two main reasons: they’re hard to target, and they’re good at suppressing the immune system.
To attack a cancer cell, you need to be able to find it. Sometimes cancer cells have more unique identifiable elements on the outside, but other times they don’t. Imagine trying to identify someone when all you know is that they’re wearing jeans.
Many of the proteins found on solid cancer cells are also present in healthy tissue, making them potentially risky targets.
Solid tumors are also good at building an environment around them that blocks and suppresses the immune system. Think of it like a protective shield.
“They prevent your immune system from recognizing and clearing aberrant cells,” Johnson said, referring to cancer cells.
Dispatch Bio’s signature treatment — called the Flare platform — is designed to overcome both of these challenges by tagging cancer cells with a unique target and boosting the immune system.
The strategy revolves around a virus that, when injected intravenously, will traverse the body in search of tumor cells. Once the virus finds its target, it’ll take up residence inside the cell and tag it with a target protein called “the Flare.”
“You can create that Flare protein to be something that is not present on healthy tissue throughout the body,” Johnson said.
In colon cancer, for example, they would use a protein that is not present on any healthy colon cell, to avoid toxicity.
At the same time, the Flare platform secretes chemical signals to re-engineer and reset the environment around the tumor. This enables the immune system to better attack the tumor.
“It is a Trojan horse,” Avanzi said, describing the virus.
When a tagged cancer cell is destroyed, it goes on to release thousands more viral particles carrying the Flare. That chain reaction helps spread the therapy’s effect across multiple sites.
In animal studies, the platform has been able to completely clear out tumors without off-target effects or toxicity.
But results in animals are often difficult to replicate in people, and the ongoing clinical trial is the first time the platform is being used in humans.
The trial
If the virus successfully paints cancer cells with the target, CAR-T cells can then find and clear them. (CAR-T therapy uses what’s called a chimeric antigen receptor, a protein that recognizes a cell as cancer based on what’s on the outside of the cell.)
The first phase of the trial involves escalating the dose of the virus alongside a standard dose of an approved CAR-T therapy to figure out the ideal regimen.
Once Dispatch determines the safest dose of the virus, they’ll move into the dose expansion phase, where they test that dose in a bigger group of patients.
“We are really trying to optimize the virus,” Avanzi said.
There is no expected timeline yet for the trial.
Dispatch is actively enrolling patients at City of Hope in California and the University of Cincinnati, and is in the process of activating four or five additional sites. They plan to open a site in Philadelphia, too.
