Specific immunotherapy against occult cancer metastases

Wang, Lu; Dong, Zhongyun; Donawho, Cherrie K.; Fidler, Isaiah J.

doi:10.1002/ijc.10494

Cited by 14 publications

(15 citation statements)

References 46 publications

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“…Several additional and/or complementary strategies have been developed to stop cancer cell proliferation and to kill them. These strategies include: an immunological approach involving inflammatory cytokines such as interferon [1,2], as well as cancer immunotherapy, which targets tumorspecific antigens that can be recognized by cytolytic T lymphocytes [3,4]; the use of factors blocking or inhibiting tumor angiogenesis [5][6][7]; the restriction of dietary calories to reduce cancer formation, most probably due to the inhibitory effect of fasting on cell proliferation, the so-called caloric restriction [8][9][10][11]; and some genetic manipulations [12].…”

Section: Cancer Definition and Strategies To Fight Against Cancermentioning

confidence: 99%

Potential Therapeutic Application of the Association of Vitamins C and K3 in Cancer Treatment

Calderón¹,

Cadrobbi

Marques

et al. 2002

CMC

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The decision of stressed cells to die or to survive is made by integrating signals at different levels through multiple check points. However, initiation and continued progression toward cell death by apoptosis in cancer cells may be blocked by mutation of the tumor suppressor p53 or overexpression of members of the bcl-2 family of proteins. The existence of such mechanisms indicates that cancer cells lose the controls regulating their cell cycle. Therefore, the activation of their programmed cell death appears as a major therapeutic target. Oxidative stress can stimulate growth, trigger apoptosis, or cause necrosis depending upon the dose and the exposure time of the oxidizing agent. A large body of evidence supports the idea that oxidative stress induced by redox cycling of vitamins C and K(3) in association surpasses cancer cellular defense systems and results in cell death. The molecular mechanisms underlying such a process are, however, still unknown. Indeed, several types of cell death may be produced, namely autoschizis, apoptosis and necrosis. Combined vitamin C and K(3) administration in vitro and in vivo produced tumor growth inhibition and increased the life-span of tumor-bearing mice. CK(3)-treatment selectively potentiated tumor chemotherapy, produced sensitization of tumors resistant to some drugs, potentiated cancer radiotherapy and caused inhibition of the development of cancer metastases without inducing toxicity in the host. We propose the association of vitamins C and K(3) as an adjuvant cancer therapy which may be introduced into human cancer therapy without any change in the classical anticancer protocols, and without any supplementary risk for patients.

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Section: Cancer Definition and Strategies To Fight Against Cancermentioning

confidence: 99%

Potential Therapeutic Application of the Association of Vitamins C and K3 in Cancer Treatment

Calderón¹,

Cadrobbi

Marques

et al. 2002

CMC

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show abstract

“…5 Cancer vaccines and other active immunotherapies are currently being explored as novel adjuvant and neoadjuvant therapies for breast cancer. A key advantage of active immunotherapies is their elaboration of tumor-specific immune responses capable of training a patient's immune system to recognize and eliminate occult tumor cells, [6][7][8] thus preventing their re-emergence at a later time. Another advantage is the durability of a tumor-specific immune response that potentially persists long after administration of the immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant immunotherapy with chitosan and interleukin-12 to control breast cancer metastasis

Yang

Kurtz

et al. 2014

OncoImmunology

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Metastasis accounts for approximately 90% of breast cancer-related deaths. Therefore, novel approaches which prevent or control breast cancer metastases are of significant clinical interest. Interleukin-12 (IL-12)-based immunotherapies have shown promise in controlling metastatic disease, yet modest responses and severe toxicities due to systemic administration of IL-12 in early trials have hindered clinical application. We hypothesized that localized delivery of IL-12 co-formulated with chitosan (chitosan/IL-12) could elicit tumor-specific immunity and provide systemic protection against metastatic breast cancer while minimizing systemic toxicity. Chitosan is a biocompatible polysaccharide derived primarily from the exoskeletons of crustaceans. In a clinically relevant resection model, mice bearing spontaneously metastatic 4T1 mammary adenocarcinomas received intratumoral injections of chitosan/IL-12, or appropriate controls, prior to tumor resection. Neoadjuvant chitosan/IL-12 immunotherapy resulted in long-term tumor-free survival in 67% of mice compared to only 24% or 0% of mice treated with IL-12 alone or chitosan alone, respectively. Antitumor responses following chitosan/IL-12 treatment were durable and provided complete protection against rechallenge with 4T1, but not RENCA renal adenocarcinoma, cells. Lymphocytes from chitosan/IL-12-treated mice demonstrated robust tumor-specific lytic activity and interferon-g production. Cell-mediated immune memory was confirmed in vivo via clinically relevant delayed-type hypersensitivity (DTH) assays. Comprehensive hematology and toxicology analyses revealed that chitosan/IL-12 induced transient, reversible leukopenia with no changes in critical organ function. Results of this study suggest that neoadjuvant chitosan/IL-12 immunotherapy prior to breast tumor resection is a promising translatable strategy capable of safely inducing to tumor-specific immunity and, in the long term, reducing breast cancer mortality due to progressive recurrences.

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“…[10][11][12][13][14][15][16][17] Moreover, we and others have shown that intralesional delivery of the IFN-b gene, which allows for the accumulation of higher intratumoral concentrations of IFN-b, is able to suppress primary tumors, prolong the survival of tumor-bearing mice, and protect against a second challenge in syngeneic mice. 12,18,19 Nitric oxide (NO) is a small molecule produced by mammalian cells. It interacts with a wide array of molecules from superoxide anion to proteins.…”

Section: Introductionmentioning

confidence: 99%

Inducible nitric oxide synthase activity is essential for inhibition of prostatic tumor growth by interferon-β gene therapy

et al. 2006

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We have previously reported that adenoviral vector-mediated interferon (IFN)-b gene therapy inhibits orthotopic growth of human prostate cancer cells in nude mice. The purpose of this study was to determine efficacy and mechanisms of this therapy in immunecompetent mice. TRAMP-C2Re3 mouse prostate cancer cells infected with 100 multiplicity of infection (MOI) Furthermore, quantitative reverse-transcriptional PCR analysis showed that AdmIFN-b therapy, in C57BL/6 but not the iNOS-null counterparts, reduced levels of the mRNAs for angiopoietin, basic fibroblast growth factor, matrix metalloproteinase-9, transforming growth factor-b1, vascular endothelial growth factor (VEGF)-A, and VEGF-B, as well as the antiapoptotic molecule endothelin-1. These data indicated that IFN-b gene therapy could be effective alternative for the treatment of locally advanced prostate cancer and suggest an obligatory role of NO in IFN-b antitumoral effects in vivo.

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Specific immunotherapy against occult cancer metastases

Cited by 14 publications

References 46 publications

Potential Therapeutic Application of the Association of Vitamins C and K3 in Cancer Treatment

Potential Therapeutic Application of the Association of Vitamins C and K3 in Cancer Treatment

Neoadjuvant immunotherapy with chitosan and interleukin-12 to control breast cancer metastasis

Inducible nitric oxide synthase activity is essential for inhibition of prostatic tumor growth by interferon-β gene therapy

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