
Stanford’s new research has developed a new synthetic molecule that combines a tumor-targeting agent with another molecule that triggers the immune system to attack the tumor. The immunotherapy can be administered intravenously and can target either a specific location or multiple tumors.
The research team has just completed testing on laboratory animals and they were able to induce complete tumor regression in half the test population infected with aggressive triple negative breast cancers with just one injection. They had similar results from a group of mice infected with pancreatic cancer.
“We essentially cured some animals with just a few injections,” said Jennifer Cochran, PhD, the Shriram Chair of the Department of Bioengineering. “It was pretty astonishing. When we looked within the tumors, we saw they went from a highly immunosuppressive microenvironment to one full of activated B and T cells — similar to what happens when the immune-stimulating molecule is injected directly into the tumor. So, we’re achieving intra-tumoral injection results but with an IV delivery.”
Building on Earlier Research. The work in this study builds on that done in 2018 by Ronald Levy, MD and Edit Saga-Barfi, PhD, both of Stanford School of Medicine. That study used the same immune-activating agent and a different one injected directly into the tumor site. The results of that trial were complete tumor eradication, elimination of distant metastases and also blocked recurrence in mammary tumors. The research group then launched a clinical trial in people with non-Hodgkin lymphoma.
“The surprising result of the new research was that the sculpting of the tumor microenvironment by this intravenously administered molecule was identical to that achieved by injecting immune stimulating agents directly into the tumor,” Levy said. “This is a big advantage because it’s no longer necessary to have an easily or safely injectable tumor site.”
Next Steps. Before any human testing can occur, much more research needs to be done. The level of optimism is high in the research team because the tumor-targeting portion of the PIP-CpG molecule (PIP) appears to recognize proteins called interns. Because these are found at high levels on the surface of many cancer types, there is a possibility for an off-the-shelf treatment for patients with a variety of cancer types.
Cochran and her team have coupled the PIP-CpG molecule with probes that can be visualized with near-infrared imaging or positron emission tomography. This gives them the tool to track the location of hard-to-see cancers.
“These integrin-targeting molecules act like guided missiles,” Cochran said. “They can deliver toxic drugs or imaging agents. Now we’re using them to deliver a signal that riles up the immune cells to fight the tumor.” That signal, CpG, mimics a pattern of DNA common in bacteria and viruses but rarely found in vertebrates.
“After more than 10 years of work on PIP, it is rewarding to experience this convergence of expertise from laboratories around Stanford, which allowed us to develop a highly promising new cancer treatment strategy,” Cochran said.