F16IL2 + BI 836858

F16IL2 + BI 836858 is a combination therapy under clinical investigation for **posttransplant relapse of acute myeloid leukemia (AML)**. F16IL2 is a recombinant antibody-cytokine fusion protein, consisting of an anti-tenascin-C (F16) antibody linked to interleukin-2 (IL-2). It delivers IL-2 selectively to the tumor microenvironment by targeting a splice isoform of tenascin-C found in leukemia-modified stroma, promoting local expansion and activation of **natural killer (NK) cells**. BI 836858 is a fully humanized, Fc-engineered IgG1 monoclonal antibody directed against **CD33**, a myeloid differentiation antigen highly expressed on most AML blasts, designed for enhanced binding to FcγRIIIA/CD16 and augmented **antibody-dependent cellular cytotoxicity (ADCC)**. The combination seeks to synergistically potentiate NK cell-mediated cytotoxicity against leukemic blasts by increasing NK cell numbers/function (via IL-2) and directing their cytotoxicity to CD33-positive cells (via BI 836858). Early phase 1 trial data show a manageable safety profile, with frequent side effects including fever, chills, and infusion reactions, and some clinical responses in heavily pretreated, post-allogeneic hematopoietic stem cell transplant (alloHSCT) AML patients[1][3].