Monocyte chemotactic cytokine gene transfer modulates macrophage infiltration, growth and susceptibility to IL-2 therapy of a murine melanoma

Bottazzi, Barbara; Walter, Sabine; Govoni, Deanna; Colotta, Francesco; Mantovani, Alberto

doi:10.1016/1043-4666(91)90468-s

Cited by 86 publications

(103 citation statements)

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“…Several previous reports have demonstrated that chemokines or costimulatory molecules induce an effective antitumor response. [26][27][28] One of the best candidates for chemokines is CCL21, which has been proposed to play a role in favoring the interactions between DCs and T cells in secondary lymphoid organs through CCR7 receptor. 4,7,9,29 In fact, mice deficient in the expression of CCL21 showed defects in lymphocyte homing and DC localization, 30 and mice lacking CCR7 receptor also had defects in lymph node architecture.…”

Section: Discussionmentioning

confidence: 99%

Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT

et al. 2004

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To establish a more efficient treatment for immunotherapy against solid tumors, we have evaluated the antitumor effect by coexpression of a chemokine CCL21/secondary lymphoid tissue chemokine and a costimulatory molecule LIGHT in colon carcinoma C26. C26 cells expressing either CCL21 or LIGHT exhibited a significantly reduced tumor growth in vivo, and mice inoculated with these cells showed a prolonged survival, but eventually all these mice died. In contrast, C26 cells expressing both CCL21 and LIGHT exhibited a minimal tumor growth in vivo, and all these mice survived healthily with a tumor remission and consequently acquired a strong protective immunity. A markedly increased infiltration of mature dendritic cells (DCs), and CD8 þ T cells was observed in the tumor mass, and their spleen cells showed a greatly enhanced cytotoxic T lymphocyte (CTL) activity against C26 tumor and interferon (IFN)-g production. Neutralization of IFN-g or depletion of CD8 þ or CD4 þ T cells significantly reduced the antitumor activity. These results suggest that the combined treatment with CCL21 and LIGHT is able to induce a synergistic antitumor effect to eradicate tumor completely by greatly enhancing tumor-infiltration of lymphocytes including mature DCs and CD8 þ T cells, resulting in markedly augmented CTL activity and IFN-g production.

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Section: Discussionmentioning

confidence: 99%

Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT

et al. 2004

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“…Infiltration of lymphocytes, macrophages and neutrophils was observed at the site of inoculation with chemokine gene transfected tumor cells. 17,18,35 Ltn is a new protein belonging to the C or ␥ subfamily of chemokines with only two of the four cysteine residues. Ltn has been shown to be a chemoattractant specific for CD8 + T cells and/or NK cells, and to be produced by CD8 + T cells, NK cells, and mast cells.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] Recent studies have illustrated that tumor cells transduced with cytokine or chemokine genes showed increased immunogenicity and decreased tumorigenicty. [15][16][17][18][19] The recently discovered chemokine lymphotactin (Ltn) is the sole member of the third subfamily of chemokines, C chemokines. Ltn has been shown to be a chemoattractant specific for T lymphocytes and/or natural killer (NK) cells.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated lymphotactin gene transfer improves therapeutic efficacy of cytosine deaminase suicide gene therapy in established murine colon carcinoma

Tao

Cheng

et al. 2000

Gene Ther

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Lymphotactin (Ltn) is the sole member of C chemokines which attracts T cells and NK cells specially. Ltn gene was transferred in vivo to improve the antitumor efficacy of cytosine deaminase (CD) gene therapy. Upregulation of CD80 and CD54 on murine CT26 colon carcinoma cells was observed after combined transfection with adenovirus encoding CD (AdCD) and adenovirus encoding murine Ltn (AdLtn) followed by administration of 5-fluorocytosine (5FC) in vitro. AdCD/5FC treatment also increased the expression of CD95 and induced obvious apoptosis of CT26 cells. After combined treatment with AdLtn and AdCD/5FC, the preestablished murine model with subcutaneous CT26 colon carcinoma exhibited most significant tumor growth inhibition, and four of eight tumor-bearing mice were tumor free, while tumors in other mice grew more progressively. Examination of lymphocyte infiltration and cytokine gene expression in

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“…On the contrary, in line with our present observations, we and other independent groups have observed that MCP-1 gene transduction alone marginally affects the growth and metastatic capacity of tumor cells when injected into mice and that other effector molecules such as IL-2, IFN-g, lipopolysaccharide or anti-P glycoprotein are frequently required to suppress tumorigenicity in vivo. [23][24][25][26][27][28] We reported that the antitumor effects of the herpes simplex virus thymidine kinase/ganciclovir system are significantly enhanced by codelivering the MCP-1 gene to hepatocellular carcinoma cells when the tumor was subcutaneously injected. 29 Moreover, we demonstrated that MCP-1 induced the migration of monocytes/macrophages around tumor cells, which were rendered apoptotic by thymidine kinase together with ganciclovir.…”

Section: Discussionmentioning

confidence: 99%

hTERT-promoter-based tumor-specific expression of MCP-1 effectively sensitizes cervical cancer cells to a low dose of cisplatin

et al. 2003

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Cervical cancers at advanced stages or with recurrent status are mainly treated by platinum-based chemotherapy, such as cisplatin. However, a novel strategy to reduce the minimally effective dose is required to prevent severe adverse effects that limit the effectiveness of the treatment. Monocyte chemoattractant protein-1 (MCP-1) is a subtype of chemokines that can promote monocyte/macrophage infiltration and enhance their phagocytosis at not only sites of inflammatory lesions but also of tumors. The present study applies MCP-1-based gene therapy to treat cervical cancers. To achieve tumor-specific expression of MCP-1, retroviral expression vector was constructed using the human telomerase reverse transcriptase gene (hTERT) promoter. Retroviral expression of MCP-1 into cervical cancer ME180 cells did not affect their proliferation either in vitro or in vivo. However, when combined with a suboptimal low dose of cisplatin, tumor formation was obviously reduced in clones transduced with MCP-1, but not in control clones. Histological examination revealed that a substantial number of macrophages infiltrated the tumor sites of MCP-1-transduced cells, but not of controls. These findings suggest that MCP-1 expression sensitizes cervical cancer cells to an otherwise ineffective low dose of cisplatin, possibly by inducing the migration of macrophages to eradicate tumor cells. This system may be a novel strategy for chemotherapy combined with immunogene therapy against otherwise intractable cervical cancers.

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Monocyte chemotactic cytokine gene transfer modulates macrophage infiltration, growth and susceptibility to IL-2 therapy of a murine melanoma

Cited by 86 publications

References 0 publications

Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT

Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT

Adenovirus-mediated lymphotactin gene transfer improves therapeutic efficacy of cytosine deaminase suicide gene therapy in established murine colon carcinoma

hTERT-promoter-based tumor-specific expression of MCP-1 effectively sensitizes cervical cancer cells to a low dose of cisplatin

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