Branched and linear PEI/DNA complexes differ in their ability to transfect cells. The greater efficiency of linear PEI might be due to an inherent kinetic instability under salt conditions. Understanding how to employ this kinetic instability of linear PEI could help in designing future vectors with greater flexibility and transfection efficiency in vivo.

Systemic application of positively charged polycation/DNA complexes has been shown to result in predominant gene expression in the lungs. Targeting gene expression to other sites, eg distant tumors, is hampered by nonspecific interactions largely due to the positive surface charge of transfection complexes. In the present study we show that the positive surface charge of PEI (25 kDa branched or 22 kDa linear)/DNA complexes can be efficiently shielded by covalently incorporating transferrin at sufficiently high densities in the complex, resulting in a dramatic decrease in nonspecific interactions, eg with erythrocytes, and decreased gene expression in the lung. Systemic application of transferrinshielded PEI/DNA complexes into A/J mice bearing subcut-

Systemic tumor-targeted gene delivery is attracting increasing attention as a promising alternative to conventional therapeutical strategies. To be considered as a viable option, however, the respective transgene has to be administered with high tumor specificity. Here, we describe novel polyethylenimine (

Vaccination using well-characterized allogeneic tumor cell lines expressing standardized doses of immunostimulatory cytokines is an attractive alternative for autologous gene-transfected tumor cell vaccines. In the present study, we show that vaccination with irradiated allogeneic K1735 (H-2 k ) or B16F10 (H-2 b ) melanoma cells induces a moderate degree of cross-protection against the M-3 melanoma (H-2 d ) in DBA/2 mice. Cross-protection against the syngeneic tumor was markedly improved when the allogeneic vaccines were transfected with the interleukin-2 (IL-2) gene. The IL-2 gene-modified allogeneic vaccines were effective for prophylactic vaccination against subsequent tumor challenge and for therapeutic vaccination against pre-existing tumor deposits, with efficacies that were comparable with that of the IL-2 gene-modified syngeneic vaccines. Cross-protection correlated with the cytotoxic activity of splenocytes against M-3 targets. Allogeneic vaccination was not effective in another model, against the B16F10 melanoma in C57BL/6 mice, irrespective of genetic modification with the IL-2 or granulocyte-macrophage colony-stimulating factor genes. Cancer Gene Therapy (2000) 7, 870 -878