Intramuscular administration of E7-transfected dendritic cells generates the most potent E7-specific anti-tumor immunity

Wang, T-L.; Ling, Morris; Im, Sungbin; T, Pham; Pai, Sara I.; Zhang, Lu; Rj, Kurman; Dm, Pardoll; Wu, Tong

doi:10.1038/sj.gt.3301160

Cited by 108 publications

(99 citation statements)

References 26 publications

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“…an important one. It is well established that DC can stimulate primary immune responses (7,10,19,25,26,63,64), and our data confirm this point. However, our data show that M⌽ can also stimulate T cells in vivo to proliferate, express effector functions, and mature into memory cells.…”

Section: Figure 10 M⌽ and Dcs Directly Stimulate Naive P-14 Cd8supporting

confidence: 80%

Both Dendritic Cells and Macrophages Can Stimulate Naive CD8 T Cells In Vivo to Proliferate, Develop Effector Function, and Differentiate into Memory Cells

Pozzi

Maciaszek

Rock

2005

The Journal of Immunology

228

207

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The generation of T cell immunity requires the acquisition and presentation of Ag on bone marrow-derived APCs. Dendritic cells (DC) are believed to be the most potent bone marrow-derived APCs, and the only ones that can stimulate naive T cells to productively respond to Ags. Because macrophages (MΦ) are bone marrow-derived APCs that are also found in tissues and lymphoid organs, can acquire and present Ag, and can express costimulatory molecules, we have investigated their potential to stimulate primary T cell responses in vivo. We find that both injected MΦ and DCs can migrate from peripheral tissues or blood into lymphoid organs. Moreover, injection of peptide-pulsed MΦ or DCs into mice stimulates CD8 T cells to proliferate, express effector functions including cytokine production and cytolysis, and differentiate into long-lived memory cells. MΦ and DCs stimulate T cells directly without requiring cross-presentation of Ag on host APCs. Therefore, more than one type of bone marrow-derived APC has the potential to prime T cell immunity. In contrast, another bone marrow-derived cell, the T lymphocyte, although capable of presenting Ag and homing to the T cell areas of lymphoid organs, is unable to stimulate primary responses. Because MΦ can be very abundant cells, especially at sites of infection and inflammation, they have the potential to play an important role in immune surveillance and the initiation of T cell immunity.

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Section: Figure 10 M⌽ and Dcs Directly Stimulate Naive P-14 Cd8supporting

confidence: 80%

Both Dendritic Cells and Macrophages Can Stimulate Naive CD8 T Cells In Vivo to Proliferate, Develop Effector Function, and Differentiate into Memory Cells

Pozzi

Maciaszek

Rock

2005

The Journal of Immunology

228

207

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“…Generation of luciferase-expressing E7-specific CD8 + T cells. An E7-specific CD8 + T cell line has been previously described (24). To generate a luciferase-expressing E7-specific CD8 + T cell line, we first created a retrovirus containing luciferase (pLuci-thy1.1 construct), which expressed both luciferase and thy1.1.…”

Section: Methodsmentioning

confidence: 99%

Ectopic Expression of Vascular Cell Adhesion Molecule-1 as a New Mechanism for Tumor Immune Evasion

Lin¹,

Lü²,

Hung³

et al. 2007

Cancer Research

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Immune escape is an important reason why the immune system cannot control tumor growth, but how escape variants emerge during immunotherapy remains poorly understood. Here, we identify a new mechanism of tumor immune escape using an in vivo selection strategy. We generated a highly immune-resistant cancer cell line (P3) by subjecting a susceptible cancer cell line (P0/TC-1) to multiple rounds of in vivo immune selection. Microarray analysis of P0 and P3 revealed that vascular cell adhesion molecule-1 (VCAM-1) is up-regulated in the P3-resistant variant. Retroviral transfer of VCAM-1 into P0 significantly increased its resistance against a vaccine-induced immune response. Analysis of tumors showed a dramatic decrease in the number of tumorinfiltrating cluster of differentiation 8 + (CD8 + ) T cells in the tumors expressing VCAM-1. In vitro transwell migration assays showed that VCAM-1 can promote the migration of CD8 + T cells through its interaction with the A 4 B 1 integrin. Site-directed mutagenesis of VCAM-1 at amino acid residues required for interaction with A 4 B 1 integrin completely abolished the immune resistance conferred by VCAM-1 in vivo. Surface staining showed that most renal cell carcinomas (RCC) express VCAM-1, whereas an RCC that responded to vaccination was VCAM-1 negative. These data provide evidence that tumor expression of VCAM-1 represents a new mechanism of immune evasion and has important implications for the development of immunotherapy for human RCC.

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“…Recent studies have demonstrated the potential use of DCs that are modified to carry tumor Ags in cancer vaccines (20). DC-based vaccines including DCs loaded with E7 peptide or proteins, DCs fused with tumor cells, and DCs transduced with the E7 gene or viral vectors have been used in cervical cancer models (21)(22)(23)(24).…”

Section: H Uman Papillomavirus (Hpv)mentioning

confidence: 99%

The Ability of Two Listeria monocytogenes Vaccines Targeting Human Papillomavirus-16 E7 to Induce an Antitumor Response Correlates with Myeloid Dendritic Cell Function

Peng

Hussain

Paterson

2004

The Journal of Immunology

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Previous work from our laboratory has shown that Lm-LLO-E7 induces complete regression of ∼75% of established TC-1 tumors, whereas Lm-E7 only slows the growth of such tumors. In this study, we examine the effects of Lm-LLO-E7 vs Lm-E7 on APCs. We hypothesize that the difference in antitumor efficacy of the two vaccines is due to the ability of each of these vectors to render immature dendritic cells (DCs) effective APCs in terms of MHC class II or costimulatory molecule expression. We also examine the ability of these vectors to stimulate cytokine production by DCs. Both vectors induced IL-12 and TNF-α, but only Lm-LLO-E7 induced IL-2 production by DCs. Lm-LLO-E7 also induced significantly higher levels of MHC class II molecules, CD40, and B7 costimulatory molecules (CD86, B7-H1, and B7-DC) on DCs than Lm-E7. Interestingly, a shift of CD11c+ cells from CD86low to CD86high is observed post-Lm-LLO-E7 infection. A similar shift is also observed for B7-H1 and B7-DC molecules. Moreover, Lm-LLO-E7, but not Lm-E7-pulsed DCs, stimulate naive T cell proliferation. These results indicate that Lm-LLO-E7 is more effective than Lm-E7 at inducing DC maturation. This effect is independent of the E7 Ag, because Lm-LLO-NP, and a mixture of Lm-LLO-NP and Lm-E7 induce the same changes in DC phenotype as Lm-LLO-E7. Taken together, the changes in DC expression correlate well with the differences in antitumor efficacy between these two vaccines.

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Intramuscular administration of E7-transfected dendritic cells generates the most potent E7-specific anti-tumor immunity

Cited by 108 publications

References 26 publications

Both Dendritic Cells and Macrophages Can Stimulate Naive CD8 T Cells In Vivo to Proliferate, Develop Effector Function, and Differentiate into Memory Cells

Both Dendritic Cells and Macrophages Can Stimulate Naive CD8 T Cells In Vivo to Proliferate, Develop Effector Function, and Differentiate into Memory Cells

Ectopic Expression of Vascular Cell Adhesion Molecule-1 as a New Mechanism for Tumor Immune Evasion

The Ability of Two Listeria monocytogenes Vaccines Targeting Human Papillomavirus-16 E7 to Induce an Antitumor Response Correlates with Myeloid Dendritic Cell Function

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