LOS ANGELES—“Surgery is a mainstream cancer treatment strategy in the clinic, which has been extensively used for most local solid tumors, such as those of the brain and breast,” explained Zhen Gu, a professor of bioengineering at the University of California, Los Angeles (UCLA) Samueli School of Engineering and member of the Jonsson Comprehensive Cancer Center. “Despite progress achieved in surgical techniques, residual tumor cells and circulating cancer cells (CTCs) often remain in the body after surgery.”
Gu is leading a team of researchers in developing a spray gel embedded with immune-boosting drugs that could help. In a peer-reviewed study, the substance was successful half of the time in triggering lab animals’ immune systems to stop the cancer from recurring and keep it from spreading to other parts of the body. A paper describing the work was published in the journal Nature Nanotechnology.
According to Gu, “The antiphagocytic ‘don’t eat me’ signal CD47, expressed in cancer cells, helps tumor cells escape myeloid cell recognition. It has emerged as a key checkpoint of innate immunity in the clinic. However, the occurrence of anemia and thrombocytopenia caused by systemic administration of these antagonists remains a concern. Our lab is interested in exploring delivery strategies for transportation and/or release of immune-checkpoint-blockade therapeutics to the surgical site.”
The researchers tested the biodegradable spray gel in mice that had advanced melanoma tumors surgically removed. They determined that the gel reduced the growth of the tumor cells that remained after surgery, which helped prevent recurrences of the cancer—after receiving the treatment, 50 percent of the mice survived for at least 60 days without their tumors recurring. Not only did the spray inhibit the recurrence of tumors from the area on the body where they were removed, but it also controlled the development of tumors in other parts of the body.
Gu, who is also a member of the California NanoSystems Institute at UCLA, explained, “The gel containing calcium carbonate nanoparticles is preloaded with the anti-CD47 antibody. The calcium carbonate nanoparticles encapsulated in the gel scavenge H+ in the surgical wound site and release CD47, thus promoting both polarization of TAMs to an M1-like phenotype and blocking the ‘don’t eat me’ signal in cancer cells and initiating the innate and adaptive immune system.”
He added that CD47, which is also known as integrin associated protein, is a transmembrane protein, found on the surface of many cells in the body. CD-47 acts as a “don't eat me” signal to macrophages of the immune system. Thus, the body uses the CD47 protein to protect cells that should be protected and to help dispose of cells that are aged or diseased. However, cancer cells also can escape macrophage recognition via up-regulation of CD47.
“This sprayable gel shows promise against one of the greatest obstacles in curing cancer,” Gu said. “One of the trademarks of cancers is that it spreads. In fact, around 90 percent of people with cancerous tumors end up dying because of tumor recurrence or metastasis. Being able to develop something that helps lower this risk for this to occur and has low toxicity is especially gratifying.”
The researchers loaded nanoparticles with an antibody specifically targeted to block CD47, a protein that cancer cells release to avoid detection. By blocking CD47, the antibody allows the immune system to find and destroy the cancer cells. The nanoparticles are made of calcium carbonate, a substance that is the main component of egg shells. Researchers chose the substance because it can be gradually dissolved in surgical wound sites and because it increases the activity of a type of macrophage that helps rid the body of foreign objects. The gel can activate T cells in the immune system to attack remaining cancer cells.
When the solution is sprayed on the surgical site, it quickly forms a gel embedded with the nanoparticles. The gel promotes wound healing, and the nanoparticles dissolve and release the anti-CD47 antibodies into the body.
While the substance will have to go through further testing and approvals before it could be used in humans, Gu and his team think the gel can be applied to the tumor resection site by surgeons immediately after the tumor is removed during surgery.
Gu concluded, “We have licensed a related technology to our start-up company, ZenCapsule Inc. for potential translation. We will further perform larger animal studies to validate both efficacy and safety before human trials.”
