Antitumor Cell-Complex Vaccines Employing Genetically Modified Tumor Cells and Fibroblasts

Abstract

The present study evaluates the immune response mediated by vaccination with cell complexes composed of irradiated B16 tumor cells and mouse fibroblasts genetically modified to produce GM-CSF. The animals were vaccinated with free B16 cells or cell complexes. We employed two gene plasmid constructions: one high producer (pMok) and a low producer (p2F). Tumor transplant was performed by injection of B16 tumor cells. Plasma levels of total IgG and its subtypes were measured by ELISA. Tumor volumes were measured and survival curves were obtained. The study resulted in a cell complex vaccine able to stimulate the immune system to produce specific anti-tumor membrane proteins (TMP) IgG. In the groups vaccinated with cells transfected with the low producer plasmid, IgG production was higher when we used free B16 cell rather than cell complexes. Nonspecific autoimmune response caused by cell complex was not greater than that induced by the tumor cells alone. Groups vaccinated with B16 transfected with low producer plasmid reached a tumor growth delay of 92% (p ≤ 0.01). When vaccinated with cell complex, the best group was that transfected with high producer plasmid, reaching a tumor growth inhibition of 56% (p ≤ 0.05). Significant survival (40%) was only observed in the groups vaccinated with free transfected B16 cells.

Combination Vaccination With Tetanus Toxoid and Enhanced Tumor-Cell Based Vaccine Against Cervical Cancer in a Mouse Model

“…The advantage of using a whole-cell vaccine, rather than a single peptide or protein as a vaccine, is that whole-cell vaccines provide all potential antigens present in the tumor cell (15)(16)(17). Whole-cell vaccines were also developed by genetically modifying the cells that express cytokines to induce an elevated immune response to the injected irradiated tumor cells (17)(18)(19). Currently available prophylactic vaccines developed from HPV virus-like particles (VLPs) against HPV-associated cervical cancer are successful in preventing tumor growth but are unsuccessful in eradicating the already infected cells (20,21).…”

An integrin-targeting nanosystem as a carrier of the selenadiazole derivative to induce ROS-mediated apoptosis in bladder cancer cells, from rational design to action mechanisms

“…33,34 PEI, another high-molecular-weight polymer that is excellent for this type of application due to its high watersolubility and controllable characteristics, has been widely used as a non-viral cationic vector for gene transfection. [35][36][37][38][39] Therefore, in this study, we used PEI to link BSeC and the RGD peptide to fabricate a cancer-targeting conjugate. In summary, this study provides a strategy for the rational design of a Se-containing, cancer-targeted theranostic agent to treat human cancer.…”