Therapeutic antitumor effects of CpG(A)-siRNAs targeting STAT3 or BCL-X_L in xenotransplanted MM and AML models. (A) IT delivery of CpG(A)-siRNAs targeting STAT3 or BCL-X_L inhibits SC growth of MV4-11 leukemia and results in augmented tumor cell death. NSG mice were challenged using 5 × 10⁶ MV4-11 cells injected SC after tumors were established (at the average diameter of 8 mm). Mice were injected IT daily using 100 μg of CpG-siRNAs as indicated. Tumor growth was measured using calipers (right). At day 16, tumors were harvested and the percentage of apoptotic annexin V⁺ tumor cells was assessed by flow cytometry (left). Statistically significant differences between CpG(A)-STAT3 or BCL-X_L siRNAs and CpG(A)-Luc RNA-treated groups (from 2-way ANOVA) are indicated by asterisks. Data are shown as means ± SEM (n = 5). (B-C) Local treatment using CpG(A)-STAT3 siRNA as in panel A, leads to STAT3 gene silencing (B and C left graphs as shown by qPCR), tumor cell death (B middle as shown by flow cytometric analysis of annexin V⁺ tumor cells), and reduced growth rate of human KMS-11 myeloma (B) and MonoMac6 leukemia (C) in NSG mice. Shown are representative results from 2 independent experiments (A-B) or from a single experiment (C) using 6 mice per treatment group.