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Immunotherapy of Acute Leukemia with Cationic Lipid DNA Complexes (JVRS‐100)
Author(s) -
Chang Stella,
Herse Zachary,
Claxton David,
Giffon Thierry,
Lewis David,
Fairman Jeffery
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1077.17
Subject(s) - leukemia , spleen , medicine , immunotherapy , immunology , acute leukemia , cytokine , peripheral blood mononuclear cell , cationic liposome , pharmacology , in vivo , immune system , biology , in vitro , genetic enhancement , biochemistry , microbiology and biotechnology , gene
Acute leukemias have long been recognized as suitable targets for immunotherapy. Administration of cationic liposome‐DNA complexes (JVRS‐100) elicits cytokines of the TH1 subset, especially IL‐12, IFN‐gamma and IFN‐alpha. These cytokines are particularly important in mediating host defense against cancer. In multiple experiments using the 32Dp210‐GFP model, intravenous dosing of JVRS‐100 prevented or significantly delayed death from leukemia when delivered between 7 and 15 days following leukemic challenge. Specifically, control animals died at ∼19 days of leukemia whereas 80% of similarly leukemia challenged but JVRS‐100 treated animals (1 ug) were alive >40 days with weekly treatment beginning at day 15 (4 days prior to expected mortality). Animals dying of leukemia had splenomegaly and leukemic infiltration of spleen and liver. The GFP expression allowed quantification of leukemia in peripheral blood (PB). At day 12 following challenge PB leukocytes were ∼30% GFP positive with either no treatment, or 0.1 ug JVRS‐100, <0.1% with 1.0 ug or 5.0 ug JVRS‐100 treatment at days 2 and 9. Furthermore there is a similar cell activation profile and cytokine response in vitro following exposure of human PBMCs to JVRS‐100 as is observed following in vivo administration of JVRS‐100 to mice, making this immunostimulation technology a promising candidate for product development and eventual clinical evaluation.