Inotuzumab Ozogamicin + Donor Lymphocyte Infusion

The combination of inotuzumab ozogamicin and donor lymphocyte infusion represents a therapeutic approach that combines targeted therapy with cellular immunotherapy. Inotuzumab ozogamicin is an antibody-drug conjugate composed of a CD22-directed humanized monoclonal IgG4 antibody linked to N-acetyl-gamma-calicheamicin, a cytotoxic agent. It works by binding to CD22-expressing tumor cells, leading to internalization of the drug-CD22 complex. Once internalized, the complex forms an endosome that fuses with lysosomes, causing hydrolytic cleavage of the linker and release of N-acetyl-gamma-calicheamicin into the cell. This cytotoxic agent binds to DNA in a sequence-specific manner, inducing double-strand DNA breaks that ultimately cause cell cycle arrest and apoptotic cell death. Donor lymphocyte infusion (DLI) is a procedure that involves collecting peripheral lymphocytes from the original stem cell donor during an apheresis procedure and infusing them into the patient. Unlike allogeneic bone marrow transplantation, DLI is not preceded by chemotherapy and T cells are not depleted. The procedure aims to stimulate a donor-versus-leukemia (GVL) reaction to eradicate malignant cells. The combination of these two approaches may represent a strategy to target B-cell malignancies through both direct cytotoxicity (inotuzumab ozogamicin) and immune-mediated effects (donor lymphocyte infusion), potentially enhancing overall efficacy in treating resistant or relapsed disease.