Potent Anti-Leukemic Activity of a Cationic Lipid-DNA Complex.

Cationic Lipid and DNA Complex (CLDC) is a chemically defined preparation of lipids and non-coding bacterial plasmid DNA able to activate antigen presenting and immune effector cells and thereby enhance cellular immune responses. We tested this preparation subcutaneously (SC) in two models of transplantable murine leukemia: 32D -(bcr-abl)p210 (leukemogenic in C3H/HEJ animals) and WEHI-3B cells (leukemogenic in BALB-C mice.) In multiple experiments using the 32Dp210 model a single SC dose of CLDC (200 ul) prevented or significantly delayed death from leukemia when delivered between -1 and 16 days from leukemic challenge. Specifically, control animals died at 28 days (SD=2.73) of leukemia whereas 20/24 similarly leukemia challenged but CLDC treated animals were alive >71 days (p<0.0001 − 4/20 animals died of leukemia). Animals dying of leukemia had swollen spleens and leukemic infiltration of spleen and liver on histopathological evaluation. Similarly Balb-C animals challenged with WEHI-3B cells died at a median of 30 days unless treated with CLDC (1 dose day 6 − 4/5 alive >day 40 p=0.0017). A green fluorescence protein (GFP) expressing subclone of 32Dp210 allowed quantitation of leukemia in peripheral blood (PB). PB leukocytes were 20% GFP positive on day 19. After CLDC on day 19, day 21 PB showed only 2% GFP. Animals receiving 32D-p210-GFP and treated with CLDC and CD8 antibody on day 19 showed higher GFP in followup and died earlier (median day 35) than animals treated with CLDC alone (>42 days) but later than animals receiving no treatment after leukemic challenge (median 23 days, p=0.0002.) See Figure below. We conclude that CLDC shows potent anti-leukemia activity in two murine models of AML. Antibody experiments suggest that CD8 positive effector cells contribute to this effect. Additional experiments are maturing and will be reported. This preparation has promise for activity in human acute leukemias. Figure Figure