Immunotherapy with dendritic cells for cancer

Ballestrero, Alberto; Boy, Davide; Morán, Eva; Cirmena, Gabriella; Brossart, Peter; Nencioni, Alessio

doi:10.1016/j.addr.2007.08.026

Cited by 57 publications

(39 citation statements)

References 91 publications

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“…4,5 In spite of their potency, the application of ex vivo DCs is so far limited by their availability. Growth of ex vivo DCs is both labour and resource intensive.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic nanoworms: towards novel synthetic dendritic cells for immunotherapy

et al. 2013

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A new class of antibody-functionalized, semi-flexible and filamentous polymers (diameter 5-10 nm, length $200 nm) with a controlled persistence length, a high degree of stereoregularity and the potential for multiple simultaneous receptor interactions has been developed. We have decorated these highly controlled, semi-stiff polymers with T cell activating anti-CD3 antibodies and analyzed their application potential as simple synthetic mimics of dendritic cells (sDCs). Our sDCs do not only activate T cells at significantly lower concentrations than free antibodies or rigid sphere-like counterparts (PLGA particles) but also induce a more robust T cell response. Our novel design further yields sDCs that are biocompatible and non-toxic. The observed increased efficacy highlights the importance of architectural flexibility and multivalency for modulating T cell response and cellular function in general.

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“…4,5 In spite of their potency, the application of ex vivo DCs is so far limited by their availability. Growth of ex vivo DCs is both labour and resource intensive.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic nanoworms: towards novel synthetic dendritic cells for immunotherapy

et al. 2013

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“…This objective is clinically relevant, as studies modulating DC numbers are in development for the treatment of patients with asthma (30,32), autoimmunity (65,68,74), organ transplantation (12,39,43), and cancer (3,11,73). It is unknown whether manipulating the number of tissue DC will alter the innate or adaptive antifungal host defense in these patients.…”

mentioning

confidence: 99%

Role of Dendritic Cells and Alveolar Macrophages in Regulating Early Host Defense against Pulmonary Infection withCryptococcus neoformans

et al. 2009

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Successful pulmonary clearance of the encapsulated yeast Cryptococcus neoformans requires a T1 adaptive immune response. This response takes up to 3 weeks to fully develop. The role of the initial, innate immune response against the organism is uncertain. In this study, an established model of diphtheria toxin-mediated depletion of resident pulmonary dendritic cells (DC) and alveolar macrophages (AM) was used to assess the contribution of these cells to the initial host response against cryptococcal infection. The results demonstrate that depletion of DC and AM one day prior to infection results in rapid clinical deterioration and death of mice within 6 days postinfection; this effect was not observed in infected groups of control mice not depleted of DC and AM. Depletion did not alter the microbial burden or total leukocyte recruitment in the lung. Mortality (in mice depleted of DC and AM) was associated with increased neutrophil and B-cell accumulation accompanied by histopathologic evidence of suppurative neutrophilic bronchopneumonia, cyst formation, and alveolar damage. Collectively, these data define an important role for DC and AM in regulating the initial innate immune response following pulmonary infection with C. neoformans. These findings provide important insight into the cellular mechanisms which coordinate early host defense against an invasive fungal pathogen in the lung.Cryptococcus neoformans, an opportunistic fungal pathogen acquired through inhalation, causes significant morbidity and mortality primarily in patients with impairments in host defense, including those with AIDS, those with lymphoid or hematological malignancies, or those receiving immunosuppressive therapy secondary to autoimmune disease or organ transplantation (31,33,60). The development of a T1 antigenspecific immune response characterized by gamma interferon production and classical activation of macrophages is required to eradicate the organism (4,8,21,23,24,28). This adaptive immune response takes 2 to 3 weeks to develop and coincides with the CCR2-mediated recruitment of additional pulmonary dendritic cells (DC) and T cells to the lung (51,66,67). The role of initial, innate immune responses against the organism (prior to the development of adaptive immunity) is not well understood.Resident lung phagocytic cells, primarily DC and alveolar macrophages (AM), are likely the first immune cells exposed to C. neoformans upon inhalation of the organism into the lung. Both DC and AM express lectin receptors, including macrophage mannose receptor and DC-specific non-ICAM3 grabbing nonintergrin (DC-SIGN) (14, 15), which bind C. neoformans glycoantigens, including mannoproteins (42, 55). DC and AM phagocytose the organism in vitro and in vivo (29,34,63,77,78), and phagocytosis (and/or exposure to soluble glycoantigens or cryptococcal DNA) is associated with cytokine and chemokine production (5,29,40,48,49,55,61) and yeast lysis (77). It is unclear whether phagocytosis by resident DC and AM contributes to early clearance and/or the la...

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“…So we hope the role of AR on DCs could be benefit for anticancer immunotherapy. 35,36 But such studies require large numbers of patients and long follow up periods to determine the impact of AR on disease free and overall survival, thus, more time is required to see the results. However a research of this investigation is now beginning in our group.…”

Section: Discussionmentioning

confidence: 99%

Maturation and upregulation of functions of murine dendritic cells (DCs) under the influence of purified Aromatic-Turmerone (AR)

Tan

Yang²,

Zhang

et al. 2012

Human Vaccines & Immunotherapeutics

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Immunotherapy with dendritic cells for cancer

Cited by 57 publications

References 91 publications

Therapeutic nanoworms: towards novel synthetic dendritic cells for immunotherapy

Therapeutic nanoworms: towards novel synthetic dendritic cells for immunotherapy

Role of Dendritic Cells and Alveolar Macrophages in Regulating Early Host Defense against Pulmonary Infection withCryptococcus neoformans

Maturation and upregulation of functions of murine dendritic cells (DCs) under the influence of purified Aromatic-Turmerone (AR)

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