CD7 Nanobody-Based Immuno-Nanotoxin for Targeted Treatment of T-Cell Acute Lymphoblastic Leukemia

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) has been plagued by high relapse and mortality rates due to the lack of available targeted treatment options in the clinic. Herein, a CD7specific immuno-nanotoxin based on anti-CD7 nanobody-modified polymersome-mertansine nanoconjugates (aCD7-Ps-DM1) was engineered to enable effective and targeted chemotherapy of orthotopic T-ALL in vivo. aCD7-Ps-DM1 with regulable aCD7 density showed no DM1 leakage while rapid DM1 release under reducing conditions. The aCD7-Ps-DM1 immuno-nanotoxin efficiently targeted CD7-positive CCRF-CEM T-ALL cells, leading to 5-fold and >13-fold greater anti-ALL activity than that of nontargeted Ps-DM1 and CD7-negative B-ALL cell lines, respectively. In orthotopic CCRF-CEM T-ALL-bearing mice, repetitive (multiple) dosing of aCD7-Ps-DM1 persistently inhibited leukemia progression and infiltration in the bone marrow, blood, and organs, leading to significantly improved survival. This CD7-specific immuno-nanotoxin may offer a potential targeted treatment strategy for T-ALL.