Augmentation of local antitumor immunity in the liver by tumor vaccine modified to secrete murine interleukin 12

Abstract

Minimal residual lesions have been a major problem in surwith the parental cells was significantly augmented in mice gical management of cancer. We transfected M5076 with vaccinated with the IL-12 transfectant compared with the murine IL-12 gene by a retroviral vector, established a control. On the other hand, both cytotoxic activity and IFNstable transfectant secreting IL-12 and investigated its anti-␥ production of spleen cells in the M5076-vaccinated and tumor effects on a spontaneous liver metastasis murine transfectant-vaccinated mice were at similar levels. Immumodel of M5076 reticulum cell sarcoma. Subcutaneous nophenotypic analysis revealed the selective increase of vaccination of the irradiated transfectant into the remote CD3 + NK1 + population in the liver from the transfectant-vacskin following the amputation of the tumor-bearing limb cinated mice. These results suggest that tumor vaccines improved survival when compared with the vaccination of genetically modified to secrete IL-12 continuously at a relairradiated parental cells (control). Cytotoxic activities tively low level preferentially augment local antitumor against parental M5076 were significantly stronger in the activity in the liver rather than systemic immune responses. hepatic lymphocytes from the mice vaccinated with the ILThis strategy warrants further investigation as an adjuvant 12 transfectant than those from the control. IFN-␥ promodality in the management of postoperative residual duction of hepatic lymphocytes when they were cocultured tumors.

Retracted: Enhanced Inhibition of Tumour Growth and Metastasis, and Induction of Antitumour Immunity by IL‐2‐IgG2b Fusion Protein

“…The ability of genetically engineered tumour cells to elicit an efficient systemic antitumour response and immune memory against challenge with parental tumour cells strongly encourages one to use them as tumour vaccines [1–5, 12, 21]. However, rejection of tumour cells engineered to release cytokine alone is not necessarily followed by establishment of systemic immunity [22].…”

Interleukin 12 Gene Transfer into Skin Distant from the Tumor Site Elicits Antimetastatic Effects Equivalent to Local Gene Transfer

“…These include the use of fibroblasts (Tahara et al, 1994;Zitvogel et al, 1995) or tumor cells (Colombo et al, 1996) transduced in vitro with IL-12 cDNA by a retroviral vector, the direct intratumoral injection of a recombinant vaccinia viral vector (Meko et al, 1995) or an adenoviral vector encoding a transgenic IL-12 protein (Chen et al, 1997;Bramson et al, 1996), and the direct intradermal or intramuscular injection of plasmid DNA expression vector encoding the IL-12 subunits (Rakmilevich et al, 1996;Tan et al, 1996). In addition to the local effect of IL-12 cDNA, some reports have demonstrated antimetastatic effects of IL-12 gene therapy in a number of murine tumor models (Caruso et al, 1996;Rodolfo et al, 1996;Lode et al, 1998;Popovic et al, 1998;Siders et al, 1998;Fuji et al, 1999;Schultz et al, 1999).…”

Overview of Tumor Cell–Based Vaccines

“…Sun et al showed that a predominately IFN-c response was seen in splenocytes of mice challenged with IL-12-secreting tumor and that the rejection was mediated by both CD4 þ and CD8 þ T cells, although depletion of both cell types does not completely abrogate the response [77]. In a liver cancer model, IL-12-secreting cells induced a CD3 þ , NK1 þ infiltrate [78] raising the possibility that innate responses also participate in the rejection of these IL-12-secreting tumors.…”