The Immunization Site of Cytokine-Secreting Tumor Cell Vaccines Influences the Trafficking of Tumor-Specific T Lymphocytes and Antitumor Efficacy against Regional Tumors

Q2 · MEDICINE

Article

Author: Chang, Chun-Jung ; Hwang, Lih-Hwa ; Tai, Kuo-Feng ; Roffler, Steve

AbstractTumor cells engineered to secrete cytokines, referred to as tumor cell vaccines, can often generate systemic antitumor immunity and, in many cases, cause tumor regression. We compared the efficacy of s.c. immunization or intrahepatic immunization of GM-CSF-expressing tumor cell vaccines on the growth of s.c. or orthotopic liver tumors. A chemically transformed hepatic epithelial cell line, GP7TB, derived from Fischer 344 rats, was used to generate tumor models and tumor cell vaccines. Our results demonstrated that two s.c. injections of an irradiated tumor cell vaccine significantly controlled the growth of s.c. tumors, but was completely ineffective against orthotopic liver tumors. Effector cell infiltration in liver tumors was markedly reduced compared with s.c. tumors. Enhanced apoptosis of some effector cells was observed in the liver tumors compared with the s.c. tumors. Furthermore, the T cells induced by s.c. immunization preferentially migrated to s.c. tumor sites, as demonstrated by adoptive transfer experiments. In contrast, intrahepatic immunization, using parental tumor cells admixed with adenoviruses carrying the GM-CSF gene, yielded significantly better therapeutic effects on the liver tumors than on the s.c. tumors. Adoptive transfer experiments further confirmed that the T cells induced by liver immunization preferentially migrated to the liver tumor sites. Our results demonstrate that distinct T cell populations are induced by different immunization routes. Thus, the homing behavior of T cells depends on the route of immunization and is an important factor determining the efficacy of immunotherapy for regional tumors.

01 Dec 1996·Journal of Cancer Research and Clinical OncologyQ3 · MEDICINE

Active specific immunotherapy of pulmonary metastasis with vaccinia melanoma oncolysate prepared from granulocyte/macrophage-colony-stimulating-factor-gene-encoded vaccinia virus

Q3 · MEDICINE

Article

Author: Xuetao Cao ; Dian Wen Ju ; Bruce Acres

Vaccinia melanoma oncolysate (VMO) prepared with recombinant vaccinia virus encoding the gene of murine granulocyte/macrophage-colony-stimulating factor (GM-CSF) was tested for its therapeutic effect on melanoma pulmonary metastasis. The murine pulmonary metastasis model was established by injecting 2 x 10(5) B16F10 melanoma cells into the tail vein of a C57BL/6 mouse. Intraperitoneal injection of VMO was performed in tumor-bearing mice 3 and 10 days after B16F10 cell inoculation. The results showed that treatment with VMO prepared with GM-CSF-gene-encoded vaccinia virus (GM-CSFVMO) significantly decreased the number of murine pulmonary metastases and prolonged the survival of the tumor-bearing mice. Lymphocytes isolated from fresh blood and spleen of GM-CSFVMO-treated mice showed higher cytolytic activity against B16F10 melanoma cells when compared with lymphocytes from the mice of other treatment groups. Natural killer activity remained unchanged in the GM-CSFVMO-treated group. Cytotoxic activities of peritoneal macrophages were found to be greatly elevated in mice treated with GM-CSFVMO. Further study illustrated that the increased tumor necrosis factor and nitric oxide release from macrophages may contribute to their cytotoxic effects. These results suggest that the tumor oncolysate vaccine prepared with GM-CSF-gene-encoded vaccinia virus has a potent therapeutic effect on tumor metastasis through the efficient induction of antitumor immunity of the host, mainly through the cytotoxic effects of cytotoxic T lymphocytes and macrophages.

Anticancer research

Recombinant vaccinia virus expressing cytokine GM-CSF as tumor vaccine.

Article

Author: Qin, H ; Manna, S ; Tripathi, P K ; Chatterjee, S K

The efficacy of a recombinant vaccinia virus (rvv-GM-CSF) expressing the granulocyte macrophage colony stimulating factor (GM-CSF) as tumor vaccine was evaluated in the murine B16-F10 melanoma model. The vaccine was prepared by infection of irradiated tumor cells with rvv-GM-CSF. Control vaccine was B-16 cells infected with a recombinant vaccinia virus expressing Escherichia coli beta-galactosidase (rvv-lacZ). Pre-vaccination of naive C57BL/6 mice later inoculated with tumor cells and treatment of mice bearing tumors with GM-CSF vaccine inhibited tumor development and prolonged survival. Lung metastasis of B-16 was also inhibited by treatment with GM-CSF vaccine. The vaccine effects appeared to be tumor cell specific. The efficacy of the vaccine was comparable to a retroviral vaccine (MFG-muGM-CSF) in this system. The vaccine was also effective when rvv-GM-CSF was directly injected into the tumor. These data suggest that this vaccine approach has potential for use in cancer treatment, especially for patients with easily accessible tumors.

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