Effective chemo-immunotherapy of L1210 leukemiain vivo using interleukin-12 combined with doxorubicin but not with cyclophosphamide, paclitaxel or cisplatin

Zagożdżon, Radosław; Gołąb, Jakub; Stokłosa, Tomasz; Giermasz, Adam; Nowicka, Dorota; Feleszko, Wojciech; Lasek, Witold; Jakóbisiak, Marek

doi:10.1002/(sici)1097-0215(19980831)77:5<720::aid-ijc10>3.0.co;2-5

Cited by 33 publications

(35 citation statements)

References 27 publications

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“…© 2007 American Association for Cancer clincancerres.aacrjournals.org Downloaded from tumor development, and preventing tumor recurrence after surgery. Others reported that systemic coadministration of doxorubicin and IL-12 recombinant protein inhibits bladder carcinoma and B16 melanoma growth and extends the survival of L1210 leukemia-bearing mice (19), but the mechanism is unknown. To discern the underlying mechanism, we established an IL-12 and doxorubicin combination treatment using i.m.…”

Section: Resultsmentioning

confidence: 99%

“…Combinations of doxorubicin with various therapeutic proteins, such as IL-2, tumor necrosis factor-a, and CNGRCtumor necrosis factor-a, or therapeutic genes, such as TRAIL, for treating tumors were tested previously (37 -41), but only a few reports examined the robust antitumor efficacy by coadministration of doxorubicin and IL-12 recombinant protein (18,19,42). Coadministration of doxorubicin and the IL-12 gene has not been explored previously.…”

Section: Discussionmentioning

confidence: 99%

“…For example, a combination of doxorubicin and IL-12 protein therapy has boosted the inhibition of tumor growth in bladder carcinoma, B16 melanoma, and L1210 leukemia models (18,19). However, the mechanism for the enhanced effect by coadministration of IL-12 and doxorubicin is largely unknown.…”

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confidence: 99%

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Doxorubicin Directs the Accumulation of Interleukin-12–Induced IFNγ into Tumors for Enhancing STAT1–Dependent Antitumor Effect

Zhu

Waguespack

Barker

et al. 2007

Clinical Cancer Research

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Purpose: To examine the mechanism by which doxorubicin plus interleukin-12 (IL-12) gene transfer induces enhanced therapeutic efficacy against tumors. Experimental Design: Tumor-bearing mice were treated with doxorubicin, IL-12^encoding plasmid DNA, doxorubicin plus IL-12^encoding plasmid DNA, or plasmid DNA control. Doxorubicin was systemically given via i.p. injection, and IL-12 was systemically expressed via i.m. injection.To show that doxorubicin enhances the accumulation of IL-12^induced IFNg into tumors and the signal transducer and activator of transcription 1 (Stat1)^dependent antitumor efficacy, the distribution of IFNg and the therapeutic end points, such asT-cell infiltration, inhibition of tumor vessel density, tumor growth inhibition, and inhibition of spontaneous tumor metastasis in wildtype and Stat1 -/-host and tumors were determined after the treatment at the indicated time points. Results: In this study, a novel mechanism was unveiled. We discovered that doxorubicin enhances the accumulation of IL-

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Doxorubicin Directs the Accumulation of Interleukin-12–Induced IFNγ into Tumors for Enhancing STAT1–Dependent Antitumor Effect

Zhu

Waguespack

Barker

et al. 2007

Clinical Cancer Research

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“…7E) and prolonged survival (data not shown) even when these mice were depleted of PMN and NK cells. To directly test whether activated M are required in antitumor effects induced by the combination of anti-CD40 ϩ CpG, we selectively inactivated M in vivo by silica administration (43). The effectiveness of silica in inhibiting M activity was confirmed by the reduction of LPSinduced weight loss in silica-treated mice (data not shown).…”

Section: Anti-cd40 and Cpg Synergize In Vivo In Inducing M-mediated Amentioning

confidence: 99%

Synergistic Activation of Macrophages via CD40 and TLR9 Results in T Cell Independent Antitumor Effects

Buhtoiarov¹,

Lum²,

Berke

et al. 2006

The Journal of Immunology

138

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We have previously shown that macrophages (Mφ) can be activated by CD40 ligation to become cytotoxic against tumor cells in vitro. Here we show that treatment of mice with agonistic anti-CD40 mAb (anti-CD40) induced up-regulation of intracellular TLR9 in Mφ and primed them to respond to CpG-containing oligodeoxynucleotides (CpG), resulting in synergistic activation. The synergy between anti-CD40 and CpG was evidenced by increased production of IFN-γ, IL-12, TNF-α, and NO by Mφ, as well as by augmented apoptogenic effects of Mφ against tumor cells in vitro. The activation of cytotoxic Mφ after anti-CD40 plus CpG treatment was dependent on IFN-γ but not TNF-α or NO, and did not require T cells and NK cells. Anti-CD40 and CpG also synergized in vivo in retardation of tumor growth in both immunocompetent and immunodeficient mice. Inactivation of Mφ in SCID/beige mice by silica treatment abrogated the antitumor effect. Taken together, our results show that Mφ can be activated via CD40/TLR9 ligation to kill tumor cells in vitro and inhibit tumor growth in vivo even in immunocompromised tumor-bearing hosts, indicating that this Mφ-based immunotherapeutic strategy may be appropriate for clinical testing.

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“…In chemotherapy, different drugs are used to kill or hinder the growth of cancer cells whereas immunotherapy is a treatment to stimulate or restore the ability of the immune system to fight against the dreaded disease. Chemoimmunotherapy [1][2][3][4] is a new approach to treat cancer using chemotherapy combined with immunotherapy. This evolving type of cancer treatment adds modified tumor portions to chemotherapy in an effort to stimulate the immune system to shrink or destroy cancer cells.…”

mentioning

confidence: 99%

Chemoimmunotherapeutic Approach to Prolonged Survival Time in Combination with Immunization and Glutamic Acid Derivatives with Antitumor Activity in Tumor-Bearing Mice

Samanta

Alam

Basu

et al. 2007

Biological & Pharmaceutical Bulletin

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Cancer is one of the major causes of death. For cancer, the general conventional treatment and standard of care for clinical oncology remains surgery followed by radiation and/or systemic chemotherapy as deemed appropriate based on the clinical findings. Chemoimmunotherapy is an approach to treat cancer where chemotherapy is given along with immunotherapy. Chemoimmunotherapy may be useful to enhance survival time in cancer by improve immunity of the patients. This approach may enhance the therapeutic efficacy. A comparative study was done to assess the therapeutic efficacy of the whole cell vaccine and the tumor extract with or without combination chemotherapy with the synthesized glutamine and glutamic acid derivatives and analogs as well as the standard drug etoposide against Ehrlich Ascites Carcinoma (EAC) cells in Swiss Albino mice. The study showed promising results with the compound 5-N-n-hexyl-2-(4-iso-butylbenzenesulphonyl)glutamine. The compound when combined with the whole cell vaccine as well as the tumor extract increases the survival time and the therapeutic efficacy which is comparable with that of standard drug etoposide.

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Effective chemo-immunotherapy of L1210 leukemiain vivo using interleukin-12 combined with doxorubicin but not with cyclophosphamide, paclitaxel or cisplatin

Cited by 33 publications

References 27 publications

Doxorubicin Directs the Accumulation of Interleukin-12–Induced IFNγ into Tumors for Enhancing STAT1–Dependent Antitumor Effect

Doxorubicin Directs the Accumulation of Interleukin-12–Induced IFNγ into Tumors for Enhancing STAT1–Dependent Antitumor Effect

Synergistic Activation of Macrophages via CD40 and TLR9 Results in T Cell Independent Antitumor Effects

Chemoimmunotherapeutic Approach to Prolonged Survival Time in Combination with Immunization and Glutamic Acid Derivatives with Antitumor Activity in Tumor-Bearing Mice

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