A convenient cancer vaccine therapy with in vivo transfer of interleukin 12 expression plasmid using gene gun technology after priming with irradiated carcinoma cells

Abstract

We studied interleukin ( IL ) -12 gene therapy using a gene gun as a new autologous vaccination strategy for cancer. In the first experiment, BALB / c mice were inoculated with syngeneic murine renal cancer cells ( Renca ) intradermally in the abdomen. This was followed by an injection of IL -12 expression plasmid using the gene gun. About 40% of the mice exhibited rejection of the tumor after the treatment and these mice also acquired immunological resistance against a secondary challenge with Renca cells. Based on these results, we examined whether antitumor activity can be potentiated when mice undergo combination treatment with intradermal inoculation of irradiated Renca cells and transfection with IL -12 gene. Inoculation of irradiated Renca cells alone was partially effective in inducing antitumor immunity, whereas the combined treatment remarkably intensified this effect. Moreover, this combined treatment inhibited tumor establishment and enhanced survival of the mice with tumor infiltration by CD4 + and CD8 + T cells, even when the treatment was started after tumor -implantation at a distant site. This antitumor effect was antigen specific and we confirmed the induction of antitumor cytotoxic T cells by this treatment. These results show that local cutaneous transfer of IL -12 expression plasmid using gene gun technology enhances systemic and specific antitumor immunity primed by irradiated tumor cells.

Intraoperative subcutaneous or intrasplenic vaccination with modified autologous tumor cells leads to enhanced survival in a mouse tumor model

“…Here, IL-12 increases cytokine production, particularly IFN-c, proliferation, and cytotoxicity. IL-12 induces a type 1 immune response and promotes specific cytotoxic T-cell responses while inhibiting the generation of Th2 cells (Nishitani et al 2002;Wang et al 1999).…”

Formalin-fixed tumor cells effectively induce antitumor immunity both in prophylactic and therapeutic conditions

“…Various methods of antigen preparation, such as irradiated tumor cells [7,8] and frozen and thawed cells [9], have been reported, as well as results indicating which method is effective in stimulating antitumor immunity and applicable in clinical practice. For example, it has been demonstrated that cell-associated antigens are presented to T cells via both major histocompatibility complex (MHC) class I and class II pathways but are not soluble forms of antigens [10].…”

Interleukin-12: An Update on its Immunological Activities, Signaling and Regulation of Gene Expression

“…Many animal studies have shown that IL-12 plus tumor vaccine was more effective and less toxic than either component alone [73][74][75][76][77][78][79]. The effects of IL-12 as a vaccine adjuvant are believed to be related to its ability to induce multiple inflammatory cytokines such as GM-CSF, TNF-α, IL-8, IL-6, IL-15 and IL-18 [80,81], and to activate NK cells [82], to enhance the function of DC such as their maturation and antigen presentation [83], and to prime naïve T cells.…”