**5. Antitumor activity of mTRAIL-expressing cells**

The antitumor activity of CD34-TRAIL+ cells has been investigated in a variety of localized and disseminated tumor models in NOD/SCID mice. Using a localized, subcutaneous multiple myeloma model (KMS-11 cell line), intravenously-injected mTRAIL-expressing cells significantly reduced tumor growth over controls as well as soluble TRAIL.1 In fact, compared with untreated controls, both CD34-TRAIL+ cells and soluble TRAIL significantly inhibited tumor growth by day 28 after tumor injection, when tumor volumes were reduced by 38% (P < .05) and 31% (P < .05), respectively. However, on day 35, CD34-TRAIL+ cells induced a 40% reduction in tumor growth over controls (4.2 ± 1.2 vs 7.0 ± 2.0 g, P < .001), whereas a 29% reduction of tumor growth was detected in mice receiving soluble TRAIL (5.0 ± 1.7 g vs 7.0 ± 2.0 g, P < .001) (Lavazza et al., 2010). Even more importantly, an efficient antitumor activity of intravenously injected mTRAIL-expressing CD34+ cells was also detected in NOD/SCID mice bearing disseminated, systemic multiple myeloma and non-Hodgkin lymphoma xenografts (Carlo-Stella et al., 2006; Carlo-Stella et al., 2007; Carlo-Stella et al., 2008). Using KMS-11 as model system, treatment of advanced-stage disease with CD34-TRAIL+ cells resulted in a significant increase of median survival over controls (83 vs 55 days, P ≤ 0.0001), with 28% of NOD/SCID mice alive and disease-free at the end of the 150-day observation period (Carlo-Stella et al., 2006).2
