Wilms’ tumor 1 (WT1) gene expression is upregulatedduring embryogenesis but is maintained at lower levels in adult tissues (Pritchard-Joneset al, 1990). But it are overexpressed in many human malignancies such as in varioussolid tumors, including lung, pancreatic, thyroid, breast, testicular, and ovariancarcinomas and melanoma, embryonic tumors, and acute myeloid leukemia (AML), chronicmyeloid leukemia (CML) cells (Inoue et al, 1994). The WT1 gene was initially identified as atumor suppressor gene (33 – 38), but on the basis of the existing evidence wefind that the WT1 gene induces the oncogenicity in normal cells (39). Anexample, leukemic and solid cancer cell growth was inhibited by treatment with WT1-specificsiRNA (42) and WT1 antisense oligomers (40,41). On the other hand, in thetransfected cells involuntary expression of the WT1 gene promoted cell growth(43 – 45) by suppressing apoptosis (47) and induced leukemia in WT1-transgenicmice (48).
High expression of the WT1 gene in solid tumors and leukemiasdesignated that the WT1 protein might be a promising tumor-associated antigen(TAA). Gaiger et al. (53) stated that immunization with the murine MHC classI-binding WT1 peptides p136 – 144, p235 – 243 and p117 – 139 persuadedWT1-specific CTLs in mice and lysed WT1-over expressing tumor cells, althoughno evidence of autoimmune toxicity was observed. Latter, Gao et al. (54) provedthat WT1 protein could well be an attractive tumor rejection antigen.Several immune therapies exist to elicit againsttumor such as dendritic cell vaccine, immune check point inhibitors and chimericantigen receptor (CAR) therapy.
But these therapies are not effective forgermline tumor cell therapy (Chaise et al, 2008).Gene therapy is a new generation of treatment in whichgenes are uses to treat cancer or any other disease. Researchers have beendeveloping different types of gene therapy to treat cancer.This therapy needs a vehicle for delivery. This delivery vehicle might be viralor non-viral. Viral vectors, such as adeno associated viralvectors, retroviral vectors, and lentiviral vectors, offer effective genetransduction and expression. Though, they have several disadvantages, includinghigh immune rejection, conceivable tumorigenicity, uncertain insertionalmutagenesis, and limited constructive sizes for gene insertion.
Thesedisadvantages have prevented translation into clinical practice. On theother hand, non viral vectors such as nanoparticles made by polymer, liposome,lipid are used for efficient gene delivery. The nano based gene delivery hassome advantages including easy to synthesis, no risk of immune rejection, conceivabletumorigenicity, and uncertain insertional mutagenesis. However, they haveseveral disadvantages, including toxicity and biocompatibility. To resolve thisproblem scientist had used water-oil emulsion as a delivery vehicle.
The water-oilemulsion is a well-known adjuvant used for a centuries. Water-oil emulsionprotects the encapsulated DNA molecule from DNase digestion and it is fully biocompatible.The emulsion is radially up taken by phagocytes which make the emulsion as apotent delivery vehicle. In this work we used water-castor oil- water emulsionto deliver mouse WT1 (mWT1) gene to the primary immunocytes. This bi-layerdemulsion molecule can efficiently induces immunocytes and maintain a balancesbetween pro-inflammatory and anti-inflammatory cytokines which is essential tomaintain the immune therapy.