CD7-Specific Polymersomal Vincristine Delivery Potentiates Chemotherapy in T-Cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an invasive hematological malignancy characterized by a high relapse rate, due to the lack of targeted therapies. Despite intensive chemotherapy having advanced treatment progress, most patients experience treatment failure and endure severe side effects. Here, a CD7-specific polymersomal vincristine delivery system was engineered on the basis of anti-CD7 nanobody-conjugated chimeric polymersomes (aCD7P-VCR) for targeted chemotherapy of T-ALL. aCD7P-VCR, with tunable aCD7 nanobody density, mediated selective targeting and potent inhibition of CD7-positive CCRF-CEM T-ALL cells, resulting in a half-maximal inhibitory concentration of 0.11 nM VCR, but caused no obvious toxicity to normal peripheral blood mononuclear cells or T cells at 10.8 nM VCR. Interestingly, aCD7P-VCR treatment substantially reduced leukemia progression and invasion in the orthotopic CCRF-CEM T-ALL model without toxic effects, leading to significantly longer survival than clinically used VCR and nontargeted P-VCR. aCD7P-VCR is expected to provide an effective and targeted therapeutic approach for T-ALL.