VX-01 Monoclonal Antibody Targets Mucormycosis by Blocking Angioinvasion
Ashraf S. Ibrahim, PhD, discusses how VX-01 prevents fungal invasion of blood vessels and enhances immune response in immunocompromised patients.
Researchers have developed VX-01, a humanized monoclonal antibody designed to target mucormycosis, a severe fungal infection predominantly affecting immunocompromised individuals. VX-01 enhances the host's immune response and prevents fungal angioinvasion, offering a promising adjunctive treatment for this often fatal disease.
Mucormycosis, caused by Mucorales fungi, poses significant risks, especially to those with weakened immune systems. In the first part of our conversation with researcher Ashraf S Ibrahim, PhD, senior investigator at the Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, he explains, “Mucormycosis is a lethal fungal infection that became more prevalent during the COVID pandemic. Many patients treated with high doses of corticosteroids, especially those with diabetes and hyperglycemia, became infected with the fungus.” The infection occurs when individuals inhale spores that are commonly found in the environment. “You can inhale it all the time,” Ibrahim adds.
People with poorly controlled diabetes and those who are neutropenic or have leukemia are at higher risk of infection. “The classic patients at high risk in the West are neutropenic or leukemic patients, and those undergoing transplants, especially bone marrow transplants,” notes Ibrahim. He emphasizes the grave nature of the disease: “The lethality is extremely high; it's a very aggressive infection that targets blood vessels.” This process, known as angioinvasion, leads to severe tissue necrosis and infarction.
Traditional antifungal therapies have limitations, which underscores the need for innovative treatments. VX-01 is the result of humanizing a murine monoclonal antibody, C2, that targets CotH proteins—key fungal invasins that help the fungus invade host cells. “Rather than just trying to kill the organism, we focused on preventing it from invading host tissues, particularly blood vessels,” explains Ibrahim. Preclinical studies have shown that VX-01 is ten times more effective in binding to these proteins than its predecessor, C2.
VX-01 does not directly kill the fungus, but instead blocks its ability to infiltrate vital tissues. “This approach reduces the ability of the infection to be angioinvasive,” Ibrahim adds. When used in combination with antifungal drugs, VX-01 has shown the best outcomes in animal models, offering a new potential strategy for treating the disease.
Safety evaluations of VX-01 reveal no detectable damage to host cells in vitro, and minimal binding to cytoplasmic proteins in human tissue cross-reactivity studies. These findings suggest that VX-01 may offer a safer alternative to existing treatments. Ibrahim shares, “In our studies, we found no detectable damage to host cells in vitro, and minimal binding to cytoplasmic proteins in human tissue cross-reactivity studies.” This is encouraging as VX-01 progresses toward clinical trials.
The rise in mucormycosis cases is due, in part, to the global diabetes epidemic and advancements in treatments for cancer and transplants, both of which can weaken the immune system. “It’s not a surprise that mucormycosis cases are increasing,” Ibrahim says. “As medical advancements improve survival rates for other diseases, we’re seeing more infections. But we need to think outside the box to tackle this issue.”
VX-01 represents a significant step forward in the development of immunotherapies for mucormycosis, which continues to be a major challenge for immunocompromised patients. As new strategies for treating this aggressive and deadly infection are explored, VX-01 could emerge as an effective adjunctive treatment.
