The New England Journal of Medicine published an article highlighting the synergizing effect of the Hu5F9-G4 (5F9) antibody when combined with Rituximab in eliminating B-cell non-Hodgkin’s lymphoma cells. The cocktail exhibited macrophage-mediated antibody-dependent cellular phagocytosis, a process through which cells basically engulf and break down particles.
5F9 is an immune checkpoint inhibitor blocking the CD47 gene which plays an important role in apoptosis (a form of programmed cell death), proliferation, adhesion, and migration. Inhibiting CD47 signaling activates an anti-tumor T-lymphocyte immune response and T-cell mediated cell killing.
Clinical trials involved 22 participants, 15 of which suffering from diffuse large B-cell lymphoma (DLBCL) while the other 7 have follicular lymphoma. All patients had received previous therapies (median of 4) and had presented resistance to Rituximab treatments.
Initial doses of 1 mg. of 5F9 per kilogram of body weight were followed by weekly maintenance administration of 10 to 30 mg. per kg. along with Rituximab. Adverse effects were minimal, generally grade 1 or 2, the most common being anemia and infusion-related reactions.
Overall, 50% of patients managed an objective response, with 36% having a complete response. The rates of objective response and complete response were 40% and 33%, respectively, among patients with DLBCL and 71% and 43%, respectively, among those with follicular lymphoma.
A median follow-up conducted at 6.2 months for patients with DLBCL and 8.1 months among those with follicular lymphoma, noted that 91% of the responses were ongoing.
Authors concluded that “The macrophage checkpoint inhibitor 5F9 combined with rituximab showed promising activity in patients with aggressive and indolent lymphoma”.
The American Cancer Society estimates that about 75,000 new cases are diagnosed each year, and overall Non-Hodgkin lymphoma accounts for about 4% of all cancers in the United States.