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Vaccine with ß-Defensin 2–Transduced Leukemic Cells Activates Innate and Adaptive Immunity to Elicit Potent Antileukemia Responses

National Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, China

Requests for reprints: Xiao-Tong Ma, National Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China. Phone: 86-22-27307940/3053; Fax: 86-22-27306542; E-mail: ma_xt{at}yahoo.com.cn.

Murine ß-defensin 2 (MBD2) is a small antimicrobial peptide of the innate immune system. Recent study showed that MBD2 could not only recruit immature dendritic cells but also activate them by Toll-like receptor 4 and thus may provide a critical link between the innate immune system and the adaptive immune response. In this report, we examined the antileukemia activity of MBD2 in a murine model of acute lymphoid leukemia (ALL) L1210. L1210 cells were engineered to secrete biologically functional MBD2. MBD2-modified L1210 (L1210-MBD2) showed significantly reduced leukemogenecity, resulting in a 80% rate of complete leukemia rejection. Inoculation of mice with L1210-MBD2 induced enhanced CTL and natural killer (NK) activity and augmented interleukin-12 and IFN- production. All the recovered mice from the inoculation showed a protective immunity to the following challenge with parental L1210 cells and generate leukemia-specific memory CTL. Vaccines with irradiated L1210-MBD2 cells could cure 50% leukemia-bearing mice. Depletion of CD8⁺ T cells but not CD4⁺ T cells completely abrogated the antileukemia activity of MBD2. Interestingly, NK cells were also required for the MBD2-mediated antileukemia response, although ALL generally display a high degree of resistance to NK-mediated lysis. Our results suggest that MBD2 can activate both innate and adaptive immunity to generate potent antileukemia response, and MBD2 immunotherapy warrants further evaluation as a potential treatment for ALL. (Cancer Res 2006; 66(2): 1169-76)

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