A recent study from the Duke Cancer Institute could signal new options for leukemia patients resistant to traditional therapies.
In their research, the investigators applied a synthesized antibody to blood samples extracted from 11 patients with chronic lymphocytic leukemia (CLL), a form of blood cancer that primarily affects the elderly. This approach was designed to target and take down complement factor H, a protective protein involved in maintaining the cancer cell's environment. Edward Patz, James and Alice Chen professor of radiology and lead author of the study, explained that by reducing CFH, the patients' blood cells became more responsive to chemotherapy than before.
Published in PLOS ONE, the team's findings follow on the heels of a 2016 study, where they found that their CFH antibodies could markedly reduce the viability of various lab-grown cancer cells.
“When the antibody was discovered in patients with lung cancer, we wondered if the body was making it to protect against metastasis and progression of the disease,” Patz said. “We tested a recombinant form of this antibody in a number of different tumor types, including CLL.”
Patz said that this study took things one step forward, using real tumor samples from several patients with leukemia. The team's rationale for choosing CLL as their first test case was two-fold, he noted.
First, CLL has tumor cells present throughout the blood, making the process of gathering patient samples more straightforward.
Beyond ease of access, Patz noted that he and his colleagues had found existing reports which had linked the CFH protein to chemotherapy-resistant forms of CLL. By shutting down CFH, the group hypothesized, CLL cells that hadn't previously benefited from chemotherapy drugs might become more susceptible.
Their study showed that using the CFH antibody was most effective with blood cells that were resistant to a particular drug, rituximab.
“Our pilot study confirmed that if CFH could be knocked out—which we accomplished by employing this antibody—the chemotherapy would then be reactivated in patients with rituximab-resistance and increase cancer cell death,” Patz said.
Patz noted that his group was the first to be successful in targeting CFH in leukemia patients, despite many other on-going efforts. Part of their success lied in how they designed the antibody, he explained.
“While some had tried using smaller [forms of antibody], they couldn’t specifically target the [CFH] protein,” he said. “We pioneered a method to target CFH so that it would have limited side effects on surrounding non-cancerous cells.”
At the cellular level, the antibody is designed to target and bind to compatible regions of CFH. By doing so, the body's natural immune system is made to recognize the protein and degrade it. The group's research ultimately shows that removing the protein from cancerous cells and tissue could be harnessed as a real therapy for patients.
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Patz has used his success with the antibody to launch Grid Therapeutics in Durham, which will be involved in manufacturing the antibody for future use. The company is set to face its first test in about 18 months, where it will try the antibody against solid tumors—such as lung cancer or bone cancer—in a Phase 1 clinical trial.