Preclinical Evaluation of “Whole” Cell Vaccines for Prophylaxis and Therapy Using a Disabled Infectious Single Cycle-Herpes Simplex Virus Vector to Transduce Cytokine Genes

摘要: The development of genetically modified "whole" tumor cell vaccines for cancer therapy relies on the efficient transduction and expression genes by vectors. In present study, we have used a disabled infectious single cycle-herpes simplex virus 2 (DISC-HSV-2) vector constructed to express cytokine or marker upon infection. DISC-HSV-2 is able infect wide range cells efficiently beta-galactosidase reporter gene, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2 genes. Gene occurred rapidly after infection cells, level production gene product (beta-galactosidase, GM-CSF, IL-2) was shown be both time-and dose-dependent. Vaccination with irradiated DISC-mGM-CSF DISC-hIL-2-infected murine resulted in greatly enhanced immunity challenge live parental compared control vaccines. When therapeutically treat existing tumors, vaccination DISC-mGM-CSF-infected significantly reduced incidence growth rates tumors when administered locally adjacent site, providing up 90% protection. prophylactic therapeutic efficacy initially using renal carcinoma model (RENCA), results were confirmed two additional models: M3 melanoma 302R sarcoma. Therapy DISC-infected RENCA failed reduce congenitally T-cell deficient (Nu+/Nu+) mice depleted CD4+ and/or CD8+ T-lymphocytes, confirming that T-helper T-cytotoxic effector arms immune response are required promote rejection. These preclinical suggest this "novel" DISC-HSV may prove efficacious developing whole-cell clinical use.