Clinical uses of GM-CSF, a critical appraisal and update

Arellano, Martha; Lonial, Sagar

doi:10.2147/btt.s1355

Cited by 48 publications

(52 citation statements)

References 125 publications

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“…9 A and B). Figure 9C depicts an SDS/PAGE gel comparison of our synthetic samples (10,20, and 21) with recombinant GM-CSF aglycone and recombinant heterogeneously glycosylated GM-CSF (Leukine). The multiple bands observed in the Leukine structure reflect the mixture of glycoforms present in this material.…”

Section: Fully Synthetic Gm-csf: Analytical Characterization and Biolmentioning

confidence: 99%

“…Administration of GM-CSF results in robust potentiation of the immune response, and clinical studies suggest that the glycoprotein may hold promise as an adjuvant for anticancer vaccines (9,10). However, studies to date have used recombinantly derived GM-CSF mixtures, and results have been inconclusive (9); perhaps such translational issues might be addressed in a more informative fashion with homogeneous GM-CSF agents.…”

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confidence: 99%

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Synthesis of granulocyte–macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material

Zhang

Johnston

Shieh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance As biologically active glycoproteins are increasingly investigated as potential therapeutic agents, there is a growing demand for the development of strategies for the synthesis of homogeneous, single-glycoform constructs for the purposes of rigorous evaluation. Currently, most glycoproteins are accessed through recombinant methods as complex mixtures of glycoforms. Granulocyte–macrophage colony-stimulating factor (GM-CSF) is an important glycoprotein therapeutic, used to stimulate the immune system following bone-marrow transplant and chemotherapy. GM-CSF is also being explored as a potential immunoadjuvant for anticancer vaccines. We have completed a chemical synthesis of homogeneous, single-glycoform GM-CSF. Through adaptation of this modular synthetic route, it will be possible to gain access to a menu of single-glycoform GM-CSF congeners for a wide range of biological studies.

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Section: Fully Synthetic Gm-csf: Analytical Characterization and Biolmentioning

confidence: 99%

mentioning

confidence: 99%

Synthesis of granulocyte–macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material

Zhang

Johnston

Shieh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…ema.europa.eu/ema/). However, these molecules are not employed to boost tumor-targeting immune responses, but rather as immunoreconstituting (G-CSF, GM-CSF) [36][37][38][39][40][41][42][43] or oncotoxic (TNF) factors. [44][45][46][47][48][49][50][51][52][53][54][55] Importantly, cytokines can cause relatively severe adverse effects (especially upon systemic administration), which de facto reflect their robust immunostimulatory activity and/or their biological pleiotropism.…”

Section: Introductionmentioning

confidence: 99%

Trial Watch—Immunostimulation with cytokines in cancer therapy

Vacchelli¹,

Aranda

Bloy³

et al. 2015

OncoImmunology

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During the past decade, great efforts have been dedicated to the development of clinically relevant interventions that would trigger potent (and hence potentially curative) anticancer immune responses. Indeed, developing neoplasms normally establish local and systemic immunosuppressive networks that inhibit tumor-targeting immune effector cells, be them natural or elicited by (immuno)therapy. One possible approach to boost anticancer immunity consists in the (generally systemic) administration of recombinant immunostimulatory cytokines. In a limited number of oncological indications, immunostimulatory cytokines mediate clinical activity as standalone immunotherapeutic interventions. Most often, however, immunostimulatory cytokines are employed as immunological adjuvants, i.e., to unleash the immunogenic potential of other immunotherapeutic agents, like tumor-targeting vaccines and checkpoint blockers. Here, we discuss recent preclinical and clinical advances in the use of some cytokines as immunostimulatory agents in oncological indications.

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“…Attempts at systemic administration of GMCSF have been limited by poor tumor penetration and toxic side effects (32). To minimize these side effects and increase the concentration of GMCSF in the tumor microenvironment, oncolytic viruses that express GMCSF have been employed.…”

Section: Oncolytic Viral Therapymentioning

confidence: 99%

Immunotherapy for malignant pleural mesothelioma: current status and future directions

Dozier¹,

Zheng²,

Adusumilli³

2017

Transl. Lung Cancer Res.

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Malignant pleural mesothelioma (MPM) has been marked historically by poor prognosis.Current standard of care for this deadly disease results in sub-optimal improvements in overall survival (OS), which has prompted researchers to explore innovative treatment alternatives. Immunotherapy is an emerging therapeutic modality that harnesses the power of the human immune system. In this review, we summarize the different methods of immunotherapy for malignant pleural mesothelioma. Using ClinicalTrials.gov we searched the terms "immunotherapy" and "immune therapy" combined with "pleural mesothelioma".Our search yielded 75 trials, among which 37 trials met our specific criteria. Our search identified immune checkpoint blockade, immunotoxin therapy, anticancer vaccines, oncolytic viral therapy, and adoptive cell therapy as the most common and pertinent methods of immunotherapy currently being assessed in clinical trials. We have reviewed the most up-to-date clinical trials involving immunotherapeutic approaches for the treatment of malignant pleural mesothelioma. In addition to highlighting some of the successes of immunotherapy, we also have identified limitations that must be overcome to improve the efficacy of these therapies.

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Clinical uses of GM-CSF, a critical appraisal and update

Cited by 48 publications

References 125 publications

Synthesis of granulocyte–macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material

Synthesis of granulocyte–macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material

Trial Watch—Immunostimulation with cytokines in cancer therapy

Immunotherapy for malignant pleural mesothelioma: current status and future directions

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