Hitting the “don’t eat me” CD47 receptor target has galvanized an army of drug developers who want to make inroads in the burgeoning field of cancer immunotherapy by offsetting immunosuppression. But in an effort to subvert side effects that can be caused by the systemic absorption of such antagonists, researchers are testing a gel that could be sprayed on patients who have undergone surgery to inhibit tumor recurrence and metastasis.
A biodegradable fibrin gel, which encapsulates calcium carbonate nanoparticles pre-loaded with an anti-CD47 antibody, was used by a team of researchers led by Zhen Gu, a professor of bioengineering at the UCLA Samueli School of Engineering. Following tumor resection in mice with advanced melanoma, the gel was sprayed on to the surgical site to curtail the growth of tumor cells that lingered despite surgery. Half the mice in the study did not see their tumors re-emerge 60 days following treatment, data showed.
Calcium carbonate — the main component of egg shells — was chosen due to its ability to be gradually dissolved in surgical wound sites, which are slightly acidic, and because it boosts macrophage activity, said the study’s lead author Qian Chen, a postdoctoral researcher at UCLA.
A plethora of drug developers including Alexo Therapeutics, Arch Oncology, Aurigene, Blink Biomedical, Celgene, Forty Seven, Novimmune, OSE Immunotherapeutics, Sorrento, Synthon Holding and Trillium Therapeutics, are developing CD47 antagonists in the hope of scrambling the “don’t eat me” signal that cancer cells are dependent on to evade macrophages.
But the occurrence of anemia and thrombocytopenia caused by systemic administration of such antagonists-in-development remains a concern, the UCLA team wrote in their peer reviewed study published in Nature Nanotechnology.
Many cancer patients undergo surgery to uproot tumors, but often the cancer re-emerges. This research suggests the immunotherapeutic fibrin gel can “awaken” the immune system by re-arming macrophages at the surgical site to chew up cancer cells.
“We also learned that the gel could activate T cells in the immune system to get them to work together as another line of attack against lingering cancer cells,” Chen added in a statement.
The team of scientists intends to test this approach in animal trials to determine the ideal mix of nanoparticles, optimal dosing and treatment frequency, before graduating to human testing.
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