Induction of ErbB-2/neu-specific protective and therapeutic antitumor immunity using genetically modified dendritic cells: enhanced efficacy by cotransduction of gene encoding IL-12

Intratumoral administration of an adenovirus expressing a kinase dead form of ErbB-2 inhibits tumor growth

“…27 Recently, we have shown dendritic cells infected with AderbB-2⌬tk could induce protective immunity against NDL tumor cell challenge and dramatically suppressed the growth of pre-existing tumors. 28 Enhanced AderbB-2⌬tk antitumor efficacy was observed in immune-competent FVB mice as compared with immune-deficient SCID Beige mice (Figure 4). These results suggest that intratumor administration of AderbB2⌬tk stimulates an immune response against ErbB-2 in addition to inhibiting ErbB-2 receptor function.…”

“…27 Recently, we have demonstrated that dendritic cells transduced ex vivo with AderbB-2⌬tk induced both protective and therapeutic immunity against tumor cells expressing ErbB-2. 28 In this study, we investigated the antitumor effects of direct intratumoral administration of a recombinant adenovirus vector expressing a kinase dead form of ErbB-2 (AderbB-2⌬tk). Expression of the kinase dead ErbB-2 down-regulates the activity of endogenous ErbB-2 and induces apoptosis both in vitro and in vivo.…”

“…28 To test whether AderbB-2⌬tk infection has any impact on the growth of ErbB-2-positive cells due to overexpression of the kinase dead form of ErbB-2, NDL cells (which express constitutively active ErbB-2) were infected at a MOI of 100 with either control vector Ad5 BHG ⌬E1/⌬E3, or AderbB-2⌬tk. As controls, normal mouse skin fibroblasts and B16F10 melanoma cells (which do not express active ErbB-2) were also infected with the same vectors.…”

Natural killer cells play a critical role in the immune response following immunization with melanoma-antigen-engineered dendritic cells

“…Splenocytes were harvested 2 weeks later, restimulated in vitro with EL4(MART1) and tested for IFN-g-producing cells in ELISPOT assays (a) and lytic activity to B16 in chromium release microcytotoxicity studies (b). competent but T and B cell-deficient SCID mice, 25,26 and NK, T, and B cell-deficient SCID/beige mice. 27 Figure 5a shows a representative tumor protection experiment, with SCID and SCID/beige mice developing tumors regardless of immunization with melanoma-antigen-engineered DC.…”

“…3 However, in this model, genetically modified DC generated antigen-specific CTL independent of NK cells. Multiple additional murine models confirmed that tumor antigen gene-modified DC directly stimulate CD8 þ CTL, usually requiring CD4 T help, [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] which was shown to be mediated by CD40 crosslinking of the DC. 27 Two reports have shown that NK1.1 þ cells may be involved in the antitumor response generated by tumor antigen gene-modified DC.…”