Vaccination with leukemia cells expressing cell-surface-associated GM-CSF blocks leukemia induction in immunocompetent mice

Ling, Xiaoyang; Wang, Y; Dietrich, Martin; Andreeff, Michael; Arlinghaus, Ralph B.

doi:10.1038/sj.onc.1209477

Cited by 9 publications

(11 citation statements)

References 29 publications

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“…Leukemic challenge of C3H/HeJ mice with BCR-ABL transfected 32D cells (32D/BCR-ABL) regularly produced death of animals between days 26 and 34 and the 32D/BA-GFP cells (an independently derived BCR-ABL clone carrying a fluorescent marker) yielded deaths somewhat earlier (day 18-26), as has been reported previously. 30 In both of these clones, animals either ill with leukemia or succumbing to leukemia showed considerable splenomegaly and histological infiltration with blastic immature progenitor cells (data not shown). The 32D/BA-GFP cells yielded circulating GFP-expressing cells detectable by flow cytometry (described below).…”

Section: Leukemogenic Cell Lines Results In Predictable Leukemic Deathmentioning

confidence: 90%

A non-coding cationic lipid DNA complex produces lasting anti-leukemic effects

Keasey

Herse

Chang

et al. 2010

Cancer Biology & Therapy

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Cationic lipid DNA complex (CLDC) is an immunostimulatory preparation that has significant anti-leukemic effects in multiple murine models of leukemia: BCR-ABL(+) myelogenous leukemia in C3H/HeJ animals and myelomonocytic leukemia in BALB/c mice. Following leukemic challenge, CLDC treatment inhibits tumor cell growth in vivo and extends survival, sometimes resulting in apparent eradication of tumor cells. CLDC induces multiple cytokines including interferon-gamma (IFNγ), and intravenous treatment results in a more rapid and robust response than subcutaneous treatment. IFNγ is induced in a dose-dependent manner, and tachyphylaxis results from repeated doses of CLDC. Tachyphylaxis of therapeutic effects is exacerbated at higher doses, thus the optimal survival benefits are seen at intermediate doses. Animals whose leukemia has been successfully treated with CLDC exhibit a survival advantage when faced with a secondary leukemic challenge, suggesting the existence of an adaptive anti-leukemic response. This work demonstrates the effectiveness of CLDC in multiple experimental leukemias and is consistent with a stimulation of a lasting TH(1) anti-leukemic immune response.

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Section: Leukemogenic Cell Lines Results In Predictable Leukemic Deathmentioning

confidence: 90%

A non-coding cationic lipid DNA complex produces lasting anti-leukemic effects

Keasey

Herse

Chang

et al. 2010

Cancer Biology & Therapy

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“…In leukemia system, Arlinghaus and colleagues expressed mbGM-CSF, and evaluated the induction of antitumor immunity and effector cells (35). The mbGM-CSF expressing leukemia cells induced antitumor immunity involving CD8+ T cells.…”

Section: Tumor Therapy Using Membrane-bound Form Of Gm-csfmentioning

confidence: 99%

Tumor Therapy Applying Membrane-bound Form of Cytokines

Kim

2009

Immune Netw

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Tumor therapy using cytokines has been developed for last two decades. Several recombinant cytokines and tumor cell vaccines produced by cytokine gene transfer have been in clinical trials, but several side effects hamper routine clinical applications. Many cytokines are originally expressed as membrane-bound form and then processed to secretory form exerting paracrine effects. Though functional differences of these two types of cytokines are elusive yet, the membrane-bound form of cytokine may exert its effects on restricted target cells as a juxtacrine, which are in physical contacts. With the efforts to improve antitumor activities of cytokines in cancer patients, developing new strategies to alleviate life-threatening side effects became an inevitable goal of tumor immunologists. Among these, tumor cell vaccines expressing cytokines as membrane-bound form on tumor cell surface have been developed by genetic engineering techniques with the hope of selective stimulation of the target cells that are in cell-to-cell contacts. In this review, recent progress of tumor cell vaccines expressing membrane-bound form of cytokines will be discussed.

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“…Tumor cells were stably transduced using a lentivirus expressing green fluorescent protein and renilla luciferase (rLUC; ref. 14).…”

Section: Methodsmentioning

confidence: 99%

Tumor Irradiation Increases the Recruitment of Circulating Mesenchymal Stem Cells into the Tumor Microenvironment

Klopp

Spaeth²,

Dembinski³

et al. 2007

Cancer Research

277

222

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Mesenchymal stem cells (MSC) migrate to and proliferate within sites of inflammation and tumors as part of the tissue remodeling process. Radiation increases the expression of inflammatory mediators that could enhance the recruitment of MSC into the tumor microenvironment. To investigate this, bilateral murine 4T1 breast carcinomas (expressing renilla luciferase) were irradiated unilaterally (1 or 2 Gy). Twentyfour hours later, 2 Â 10 5 MSC-expressing firefly luciferase were injected i.v. Mice were then monitored with bioluminescent imaging for expression of both renilla (tumor) and firefly (MSC) luciferase. Forty-eight hours postirradiation, levels of MSC engraftment were 34% higher in tumors receiving 2 Gy (P = 0.004) than in the contralateral unirradiated limb. Immunohistochemical staining of tumor sections from mice treated unilaterally with 2 Gy revealed higher levels of MSC in the parenchyma of radiated tumors, whereas a higher proportion of MSC remained vasculature-associated in unirradiated tumors. To discern the potential mediators involved in MSC attraction, in vitro migration assays showed a 50% to 80% increase in MSC migration towards conditioned media from 1 to 5 Gy-irradiated 4T1 cells compared with unirradiated 4T1 cells. Irradiated 4T1 cells had increased expression of the cytokines, transforming growth factor-B1, vascular endothelial growth factor, and platelet-derived growth factor-BB, and this up-regulation was confirmed by immunohistochemistry in tumors irradiated in vivo. Interestingly, the chemokine receptor CCR2 was found to be up-regulated in MSC exposed to irradiated tumor cells and inhibition of CCR2 led to a marked decrease of MSC migration in vitro. In conclusion, clinically relevant low doses of irradiation increase the tropism for and engraftment of MSC in the tumor microenvironment. [Cancer Res 2007;67(24):11687-95]

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Vaccination with leukemia cells expressing cell-surface-associated GM-CSF blocks leukemia induction in immunocompetent mice

Cited by 9 publications

References 29 publications

A non-coding cationic lipid DNA complex produces lasting anti-leukemic effects

A non-coding cationic lipid DNA complex produces lasting anti-leukemic effects

Tumor Therapy Applying Membrane-bound Form of Cytokines

Tumor Irradiation Increases the Recruitment of Circulating Mesenchymal Stem Cells into the Tumor Microenvironment

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