Humoral immune response against melanoma antigens induced by vaccination with cytokine gene‐modified autologous tumor cells

Ehlken, Hanno; Schadendorf, Dirk; Eichmüller, Stefan B.

doi:10.1002/ijc.11537

Cited by 25 publications

(22 citation statements)

References 33 publications

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“…Therefore, IL-7 has been considered a master regulator of T cell homeostasis, and clinical trials are underway to evaluate the immunotherapeutic benefits of IL-7 therapy in humans (11)(12)(13)(14). However, our understanding of the factors that influence the immunological effects of exogenous IL-7 administration is sorely incomplete.…”

Section: Discussionmentioning

confidence: 99%

“…Because IL-7 is integral to the survival of naive and memory T cells, it is not surprising that several human clinical trials are in progress to evaluate the therapeutic benefits of IL-7 administration in chronic viral infections, cancer, and lymphopenia (11)(12)(13)(14). Mice and primates tolerate IL-7 therapy with no detectable side effects, and IL-7 treatment in animal models of cancer and chronic viral infection has provided encouraging results (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice

Nanjappa

Walent

Morre³

et al. 2008

J. Clin. Invest.

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IL-7 is integral to the generation and maintenance of CD8 + T cell memory, and insufficient IL-7 is believed to limit survival and the persistence of memory CD8 + T cells. Here, we show that during the mouse T cell response to lymphocytic choriomeningitis virus, IL-7 enhanced the number of memory CD8 + T cells when its administration was restricted to the contraction phase of the response. Likewise, IL-7 administration during the contraction phase of the mouse T cell response to vaccinia virus or a DNA vaccine potentiated antigen-specific CD8 + memory T cell proliferation and function. Qualitatively, CD8 + T cells from IL-7-treated mice exhibited superior recall responses and improved viral control. IL-7 treatment during the memory phase stimulated a marked increase in the number of memory CD8 + T cells, but the effects were transient. IL-7 therapy during contraction of the secondary CD8 + T cell response also expanded the pool of memory CD8 + T cells. Collectively, our studies show differential effects of IL-7 on memory CD8 + T cell homeostasis and underscore the importance of the timing of IL-7 therapy to effectively improve CD8 + T cell memory and protective immunity. These findings may have implications in the clinical use of IL-7 as an immunotherapeutic agent to bolster vaccineinduced CD8 + T cell memory.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice

Nanjappa

Walent

Morre³

et al. 2008

J. Clin. Invest.

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“…Upon phagocytosis of apoptotic melanoma cells, DCs induce a strengthened specific immune response (Shaif-Muthana et al, 2000). This effect is already used for tumour vaccination (Ehlken et al, 2004), and melanoma patients vaccinated with mature DCs showed significant tumour regression (Hersey et al, 2004;Rescigno et al, 2004). Furthermore, the tumour-induced reduction of DC number and activity in the sentinel lymph node, which increases the risk for metastasis (Vuylsteke et al, 2004), was diminished by preoperative local injection of granulocytemacrophage colony-stimulating factor, significantly improving the patient's prognosis (Vuylsteke et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model

et al. 2007

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This study investigates the effects of mistletoe lectin-I (ML-I) on melanoma growth and spread in vivo. The human melanoma cell line MV3 was xenografted into severe combined immunodeficient mice and vehicle solution or purified ML-I was administered at 30, 150 and 500 ng per kg body weight (20 mice per group) daily. After 19 days, mice were killed, primary tumours (PTs) and lungs were dissected out, and tumour weights, number of lung metastases (LMs), number of tumour-infiltrating dendritic cells (DCs), and apoptosis rates in the melanoma cells and in the DCs were assessed. A 35% reduction of PT weight (P ¼ 0.03) and a 55% decrease in number of LMs (P ¼ 0.016) were evident for low-dose ML-I (30 ng kg À1 ) treatment but not for higher doses. Mistletoe lectin-I increased apoptosis rates in the melanoma cells of PTs at all doses, while no induction of apoptosis was noted in the LMs. Low-dose ML-I significantly increased the number of DCs infiltrating the PTs (Po0.0001) and protected DCs against apoptosis, while higher doses induced apoptosis in the DCs (Po0.01). Our results demonstrate that low-dose ML-I reduced melanoma growth and number of metastases in vivo, primarily due to immunomodulatory effects.

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“…Two previous reports have used the SEREX approach to examine self-tumor Ag repertoire and their expression enhanced by IFN-␥ focusing on conventional rather than cryptic Ags (61)(62)(63). By applying the SEREX technique to screen a human testis expression cDNA library with sera from PV patients, we have identified a novel SEREX Ag that elicits potent humoral immune responses in a subset of patients with MPD.…”

Section: Discussionmentioning

confidence: 99%

An Unconventional Antigen Translated by a Novel Internal Ribosome Entry Site Elicits Antitumor Humoral Immune Reactions

Xiong

Liu

Yan

et al. 2006

The Journal of Immunology

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Self-tumor Ags that elicit antitumor immune responses in responses to IFN-α stimulation remain poorly defined. We screened a human testis cDNA library with sera from three polycythemia vera patients who responded to IFN-α and identified a novel Ag, MPD6. MPD6 belongs to the group of cryptic Ags without conventional genomic structure and is encoded by a cryptic open reading frame located in the 3′-untranslated region of myotrophin mRNA. MPD6 elicits IgG Ab responses in a subset of polycythemia vera patients, as well as patients with chronic myelogenous leukemia and prostate cancer, suggesting that it is broadly immunogenic. The expression of myotrophin-MPD6 transcripts was up-regulated in some tumor cells, but only slightly increased in K562 cells in response to IFN-α treatment. By using bicistronic reporter constructs, we showed that the translation of MPD6 was mediated by a novel internal ribosome entry site (IRES) upstream of the MPD6 reading frame. Furthermore, the MPD6-IRES-mediated translation, but not myotrophin-MPD6 transcription, was significantly up-regulated in response to IFN-α stimulation. These findings demonstrate that a novel IRES-mediated mechanism may be responsible for the translation of unconventional self-Ag MPD6 in responsive to IFN-α stimulation. The eliciting antitumor immune response against unconventional Ag MPD6 in patients with myeloproliferative diseases suggests MPD6 as a potential target of novel immunotherapy.

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Humoral immune response against melanoma antigens induced by vaccination with cytokine gene‐modified autologous tumor cells

Cited by 25 publications

References 33 publications

Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice

Effects of IL-7 on memory CD8+ T cell homeostasis are influenced by the timing of therapy in mice

Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model

An Unconventional Antigen Translated by a Novel Internal Ribosome Entry Site Elicits Antitumor Humoral Immune Reactions

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