The Experts below are selected from a list of 2742 Experts worldwide ranked by ideXlab platform
Radek Spisek - One of the best experts on this subject based on the ideXlab platform.
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Trial Watch: Immunostimulation with recombinant cytokines for cancer therapy
OncoImmunology, 2018Co-Authors: Elena García-martínez, Fernando Aranda, Aitziber Buque, Jitka Fucikova, Melody Smith, Francisco Ayala De La Peña, Alejandra Ivars, Manuel Cánovas, Ma Angeles Vicente Conesa, Radek SpisekAbstract:Cytokines regulate virtually aspects of innate and adaptive immunity, including the initiation, execution and extinction of tumor-targeting immune responses. Over the past three decades, the possibility of using recombinant cytokines as a means to elicit or boost clinically relevant anticancer immune responses has attracted considerable attention. However, only three cytokines have been approved so far by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, namely, recombinant interleukin (IL)-2 and two variants of recombinant interferon alpha 2 (IFN-α2a and IFN-α2b). Moreover, the use of these cytokines in the clinics is steadily decreasing, mostly as a consequence of: (1) the elevated pleiotropism of IL-2, IFN-α2a and IFN-α2b, resulting in multiple unwarranted effects; and (2) the development of highly effective immunostimulatory therapeutics, such as immune checkpoint blockers. Despite this and other obstacles, research in the field continues as alternative cytokines with restricted effects on specific cell populations are being evaluated. Here, we summarize research preclinical and clinical developments on the use of recombinant cytokines for Immunostimulation in cancer patients.
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trial watch Immunostimulation with toll like receptor agonists in cancer therapy
OncoImmunology, 2016Co-Authors: Kristina Iribarren, Norma Bloy, Aitziber Buque, Isabelle Cremer, Alexander M M Eggermont, Wolf Herve Fridman, Jitka Fucikova, Jerome Galon, Radek Spisek, Laurence ZitvogelAbstract:Accumulating preclinical evidence indicates that Toll-like receptor (TLR) agonists efficiently boost tumor-targeting immune responses (re)initiated by most, if not all, paradigms of anticancer immunotherapy. Moreover, TLR agonists have been successfully employed to ameliorate the efficacy of various chemotherapeutics and targeted anticancer agents, at least in rodent tumor models. So far, only three TLR agonists have been approved by regulatory agencies for use in cancer patients. Moreover, over the past decade, the interest of scientists and clinicians in these immunostimulatory agents has been fluctuating. Here, we summarize recent advances in the preclinical and clinical development of TLR agonists for cancer therapy.
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trial watch Immunostimulation with cytokines in cancer therapy
OncoImmunology, 2016Co-Authors: Erika Vacchelli, Fernando Aranda, Norma Bloy, Aitziber Buque, Isabelle Cremer, Alexander M M Eggermont, Wolf Herve Fridman, Jitka Fucikova, Jerome Galon, Radek SpisekAbstract: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.
Laurence Zitvogel - One of the best experts on this subject based on the ideXlab platform.
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Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors
Nature Reviews Clinical Oncology, 2020Co-Authors: Lorenzo Galluzzi, Laurence Zitvogel, Aitziber Buque, Juliette Humeau, Guido KroemerAbstract:Conventional chemotherapeutics have been developed into clinically useful agents based on their ability to preferentially kill malignant cells, generally owing to their elevated proliferation rate. Nonetheless, the clinical activity of various chemotherapies is now known to involve the stimulation of anticancer immunity either by initiating the release of immunostimulatory molecules from dying cancer cells or by mediating off-target effects on immune cell populations. Understanding the precise immunological mechanisms that underlie the efficacy of chemotherapy has the potential not only to enable the identification of superior biomarkers of response but also to accelerate the development of synergistic combination regimens that enhance the clinical effectiveness of immune checkpoint inhibitors (ICIs) relative to their effectiveness as monotherapies. Indeed, accumulating evidence supports the clinical value of combining appropriately dosed chemotherapies with ICIs. In this Review, we discuss preclinical and clinical data on the immunostimulatory effects of conventional chemotherapeutics in the context of ICI-based immunotherapy.
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trial watch Immunostimulation with toll like receptor agonists in cancer therapy
OncoImmunology, 2016Co-Authors: Kristina Iribarren, Norma Bloy, Aitziber Buque, Isabelle Cremer, Alexander M M Eggermont, Wolf Herve Fridman, Jitka Fucikova, Jerome Galon, Radek Spisek, Laurence ZitvogelAbstract:Accumulating preclinical evidence indicates that Toll-like receptor (TLR) agonists efficiently boost tumor-targeting immune responses (re)initiated by most, if not all, paradigms of anticancer immunotherapy. Moreover, TLR agonists have been successfully employed to ameliorate the efficacy of various chemotherapeutics and targeted anticancer agents, at least in rodent tumor models. So far, only three TLR agonists have been approved by regulatory agencies for use in cancer patients. Moreover, over the past decade, the interest of scientists and clinicians in these immunostimulatory agents has been fluctuating. Here, we summarize recent advances in the preclinical and clinical development of TLR agonists for cancer therapy.
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the secret ally Immunostimulation by anticancer drugs
Nature Reviews Drug Discovery, 2012Co-Authors: Lorenzo Galluzzi, Laurence Zitvogel, Laura Senovilla, Guido KroemerAbstract:A crucial role of the immune system in cancer progression and response to therapy has recently emerged. Here, Galluzzi and colleagues discuss the immune parameters that may predict the therapeutic response of patients to chemotherapeutics, and review the mechanisms by which current antineoplastic agents activate the immune system against cancer.
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anticancer effects of imatinib via Immunostimulation
Nature Medicine, 2011Co-Authors: Laurence Zitvogel, Guido KroemerAbstract:Imatinib represents the quintessential example of a targeted anticancer agent that directly suppresses the activation of oncogenic tyrosine kinases. Surprisingly, in the context of gastrointestinal stromal tumors (GISTs), the therapeutic effect of imatinib crucially depends on the reactivation of an anticancer immune response (pages 1094–1100 ).
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anticancer immunochemotherapy using adjuvants with direct cytotoxic effects
Journal of Clinical Investigation, 2009Co-Authors: Laurence Zitvogel, Guido KroemerAbstract:Conventional chemotherapeutics may induce immunogenic cancer cell death or stimulate immune effectors via so-called off-target effects. The study by Besch et al. in this issue of the JCI now demonstrates that agents designed to stimulate the innate immune system by activating intracellular pattern recognition receptors can kill cancer cells in a direct, cell-autonomous fashion (see the related article beginning on page 2399). The authors show that ligation of viral RNA sensors, such as RIG-I or MDA-5, by viral RNA mimetics triggers mitochondrial apoptosis in human melanoma cells in an IFN-independent fashion. The data suggest that tumor cell killing and Immunostimulation may synergize for optimal anticancer immunochemotherapy.
Aitziber Buque - One of the best experts on this subject based on the ideXlab platform.
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Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors
Nature Reviews Clinical Oncology, 2020Co-Authors: Lorenzo Galluzzi, Laurence Zitvogel, Aitziber Buque, Juliette Humeau, Guido KroemerAbstract:Conventional chemotherapeutics have been developed into clinically useful agents based on their ability to preferentially kill malignant cells, generally owing to their elevated proliferation rate. Nonetheless, the clinical activity of various chemotherapies is now known to involve the stimulation of anticancer immunity either by initiating the release of immunostimulatory molecules from dying cancer cells or by mediating off-target effects on immune cell populations. Understanding the precise immunological mechanisms that underlie the efficacy of chemotherapy has the potential not only to enable the identification of superior biomarkers of response but also to accelerate the development of synergistic combination regimens that enhance the clinical effectiveness of immune checkpoint inhibitors (ICIs) relative to their effectiveness as monotherapies. Indeed, accumulating evidence supports the clinical value of combining appropriately dosed chemotherapies with ICIs. In this Review, we discuss preclinical and clinical data on the immunostimulatory effects of conventional chemotherapeutics in the context of ICI-based immunotherapy.
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Trial Watch: Immunostimulation with recombinant cytokines for cancer therapy
OncoImmunology, 2018Co-Authors: Elena García-martínez, Fernando Aranda, Aitziber Buque, Jitka Fucikova, Melody Smith, Francisco Ayala De La Peña, Alejandra Ivars, Manuel Cánovas, Ma Angeles Vicente Conesa, Radek SpisekAbstract:Cytokines regulate virtually aspects of innate and adaptive immunity, including the initiation, execution and extinction of tumor-targeting immune responses. Over the past three decades, the possibility of using recombinant cytokines as a means to elicit or boost clinically relevant anticancer immune responses has attracted considerable attention. However, only three cytokines have been approved so far by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, namely, recombinant interleukin (IL)-2 and two variants of recombinant interferon alpha 2 (IFN-α2a and IFN-α2b). Moreover, the use of these cytokines in the clinics is steadily decreasing, mostly as a consequence of: (1) the elevated pleiotropism of IL-2, IFN-α2a and IFN-α2b, resulting in multiple unwarranted effects; and (2) the development of highly effective immunostimulatory therapeutics, such as immune checkpoint blockers. Despite this and other obstacles, research in the field continues as alternative cytokines with restricted effects on specific cell populations are being evaluated. Here, we summarize research preclinical and clinical developments on the use of recombinant cytokines for Immunostimulation in cancer patients.
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trial watch Immunostimulation with toll like receptor agonists in cancer therapy
OncoImmunology, 2016Co-Authors: Kristina Iribarren, Norma Bloy, Aitziber Buque, Isabelle Cremer, Alexander M M Eggermont, Wolf Herve Fridman, Jitka Fucikova, Jerome Galon, Radek Spisek, Laurence ZitvogelAbstract:Accumulating preclinical evidence indicates that Toll-like receptor (TLR) agonists efficiently boost tumor-targeting immune responses (re)initiated by most, if not all, paradigms of anticancer immunotherapy. Moreover, TLR agonists have been successfully employed to ameliorate the efficacy of various chemotherapeutics and targeted anticancer agents, at least in rodent tumor models. So far, only three TLR agonists have been approved by regulatory agencies for use in cancer patients. Moreover, over the past decade, the interest of scientists and clinicians in these immunostimulatory agents has been fluctuating. Here, we summarize recent advances in the preclinical and clinical development of TLR agonists for cancer therapy.
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trial watch Immunostimulation with cytokines in cancer therapy
OncoImmunology, 2016Co-Authors: Erika Vacchelli, Fernando Aranda, Norma Bloy, Aitziber Buque, Isabelle Cremer, Alexander M M Eggermont, Wolf Herve Fridman, Jitka Fucikova, Jerome Galon, Radek SpisekAbstract: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.
Thomas G Evans - One of the best experts on this subject based on the ideXlab platform.
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dose finding for new vaccines the role for Immunostimulation immunodynamic modelling
Journal of Theoretical Biology, 2019Co-Authors: Sophie J Rhodes, Gwenan M Knight, Richard G White, Denise E Kirschner, Thomas G EvansAbstract:Current methods to optimize vaccine dose are purely empirically based, whereas in the drug development field, dosing determinations use far more advanced quantitative methodology to accelerate decision-making. Applying these established methods in the field of vaccine development may reduce the currently large clinical trial sample sizes, long time frames, high costs, and ultimately have a better potential to save lives. We propose the field of Immunostimulation/immunodynamic (IS/ID) modelling, which aims to translate mathematical frameworks used for drug dosing towards optimizing vaccine dose decision-making. Analogous to Pharmacokinetic/Pharmacodynamic (PK/PD) modelling, the mathematical description of drug distribution (PK) and effect (PD) in host, IS/ID modelling approaches apply mathematical models to describe the underlying mechanisms by which the immune response is stimulated by vaccination (IS) and the resulting measured immune response dynamics (ID). To move IS/ID modelling forward, existing datasets and further data on vaccine allometry and dose-dependent dynamics need to be generated and collate, requiring a collaborative environment with input from academia, industry, regulators, governmental and non-governmental agencies to share modelling expertise, and connect modellers to vaccine data.
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dose finding for new vaccines the role for Immunostimulation immunodynamic modelling
arXiv: Quantitative Methods, 2018Co-Authors: Sophie J Rhodes, Gwenan M Knight, Richard G White, Denise E Kirschner, Thomas G EvansAbstract:Current methods to optimize vaccine dose are purely empirically based, whereas in the drug development field, dosing determinations use far more advanced quantitative methodology to accelerate decision-making. Applying these established methods in the field of vaccine development may reduce the currently large clinical trial sample sizes, long time frames, high costs, and ultimately have a better potential to save lives. We propose the field of Immunostimulation/immunodynamic (IS/ID) modelling, which aims to translate mathematical frameworks used for drug dosing towards optimizing vaccine dose decision-making. Analogous to PK/PD modelling, IS/ID modelling approaches apply mathematical models to describe the underlying mechanisms by which the immune response is stimulated by vaccination (IS) and the resulting measured immune response dynamics (ID). To move IS/ID modelling forward, existing datasets and further data on vaccine allometry and dose-dependent dynamics need to be generated and collate, requiring a collaborative environment with input from academia, industry, regulators, governmental and non-governmental agencies to share modelling expertise, and connect modellers to vaccine data.
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using vaccine Immunostimulation immunodynamic modelling methods to inform vaccine dose decision making
NPJ Vaccines, 2018Co-Authors: Sophie J Rhodes, Jeremie Guedj, Helen A Fletcher, Thomas Lindenstrom, Thomas J Scriba, Thomas G Evans, Gwenan M Knight, Richard G WhiteAbstract:Unlike drug dose optimisation, mathematical modelling has not been applied to vaccine dose finding. We applied a novel Immunostimulation/Immunodynamic mathematical modelling framework to translate multi-dose TB vaccine immune responses from mice, to predict most immunogenic dose in humans. Data were previously collected on IFN-γ secreting CD4+ T cells over time for novel TB vaccines H56 and H1 adjuvanted with IC31 in mice (1 dose groups (0.1-1.5 and 15 μg H56 + IC31), 45 mice) and humans (1 dose (50 μg H56/H1 + IC31), 18 humans). A two-compartment mathematical model, describing the dynamics of the post-vaccination IFN-γ T cell response, was fitted to mouse and human data, separately, using nonlinear mixed effects methods. We used these fitted models and a vaccine dose allometric scaling assumption, to predict the most immunogenic human dose. Based on the changes in model parameters by mouse H56 + IC31 dose and by varying the H56 dose allometric scaling factor between mouse and humans, we established that, at a late time point (224 days) doses of 0.8-8 μg H56 + IC31 in humans may be the most immunogenic. A 0.8-8 μg of H-series TB vaccines in humans, may be as, or more, immunogenic, as larger doses. The Immunostimulation/Immunodynamic mathematical modelling framework is a novel, and potentially revolutionary tool, to predict most immunogenic vaccine doses, and accelerate vaccine development.
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using data from macaques to predict gamma interferon responses after mycobacterium bovis bcg vaccination in humans a proof of concept study of Immunostimulation immunodynamic modeling methods
Clinical and Vaccine Immunology, 2017Co-Authors: Sophie J Rhodes, Helen A Fletcher, Thomas G Evans, Gwenan M Knight, Charlotte Sarfas, Andrew D White, Ansar A Pathan, Helen Mcshane, Sally SharpeAbstract:Macaques play a central role in the development of human tuberculosis (TB) vaccines. Immune and challenge responses differ across macaque and human subpopulations. We used novel Immunostimulation/immunodynamic modeling methods in a proof-of-concept study to determine which macaque subpopulations best predicted immune responses in different human subpopulations. Data on gamma interferon (IFN-γ)-secreting CD4+ T cells over time after recent Mycobacterium bovis BCG vaccination were available for 55 humans and 81 macaques. Human population covariates were baseline BCG vaccination status, time since BCG vaccination, gender, and the monocyte/lymphocyte cell count ratio. The macaque population covariate was the colony of origin. A two-compartment mathematical model describing the dynamics of the IFN-γ T cell response after BCG vaccination was calibrated to these data using nonlinear mixed-effects methods. The model was calibrated to macaque and human data separately. The association between subpopulations and the BCG immune response in each species was assessed. The macaque subpopulations that best predicted immune responses in different human subpopulations were identified using Bayesian information criteria. We found that the macaque colony and the human baseline BCG status were significantly (P < 0.05) associated with the BCG-induced immune response. For humans who were BCG naive at baseline, Indonesian cynomolgus macaques and Indian rhesus macaques best predicted the immune response. For humans who had already been BCG vaccinated at baseline, Mauritian cynomolgus macaques best predicted the immune response. This work suggests that the immune responses of different human populations may be best modeled by different macaque colonies, and it demonstrates the potential utility of Immunostimulation/immunodynamic modeling to accelerate TB vaccine development.
Guido Kroemer - One of the best experts on this subject based on the ideXlab platform.
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Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors
Nature Reviews Clinical Oncology, 2020Co-Authors: Lorenzo Galluzzi, Laurence Zitvogel, Aitziber Buque, Juliette Humeau, Guido KroemerAbstract:Conventional chemotherapeutics have been developed into clinically useful agents based on their ability to preferentially kill malignant cells, generally owing to their elevated proliferation rate. Nonetheless, the clinical activity of various chemotherapies is now known to involve the stimulation of anticancer immunity either by initiating the release of immunostimulatory molecules from dying cancer cells or by mediating off-target effects on immune cell populations. Understanding the precise immunological mechanisms that underlie the efficacy of chemotherapy has the potential not only to enable the identification of superior biomarkers of response but also to accelerate the development of synergistic combination regimens that enhance the clinical effectiveness of immune checkpoint inhibitors (ICIs) relative to their effectiveness as monotherapies. Indeed, accumulating evidence supports the clinical value of combining appropriately dosed chemotherapies with ICIs. In this Review, we discuss preclinical and clinical data on the immunostimulatory effects of conventional chemotherapeutics in the context of ICI-based immunotherapy.
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effects of interleukin 2 in Immunostimulation and immunosuppression
Journal of Experimental Medicine, 2020Co-Authors: Jonathan Pol, Pamela Caudana, Juliette Paillet, Eliane Piaggio, Guido KroemerAbstract:Historically, interleukin-2 (IL-2) was first described as an immunostimulatory factor that supports the expansion of activated effector T cells. A layer of sophistication arose when regulatory CD4+ T lymphocytes (Tregs) were shown to require IL-2 for their development, homeostasis, and immunosuppressive functions. Fundamental distinctions in the nature and spatiotemporal expression patterns of IL-2 receptor subunits on naive/memory/effector T cells versus Tregs are now being exploited to manipulate the immunomodulatory effects of IL-2 for therapeutic purposes. Although high-dose IL-2 administration has yielded discrete clinical responses, low-dose IL-2 as well as innovative strategies based on IL-2 derivatives, including "muteins," immunocomplexes, and immunocytokines, are being explored to therapeutically enhance or inhibit the immune response.
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the secret ally Immunostimulation by anticancer drugs
Nature Reviews Drug Discovery, 2012Co-Authors: Lorenzo Galluzzi, Laurence Zitvogel, Laura Senovilla, Guido KroemerAbstract:A crucial role of the immune system in cancer progression and response to therapy has recently emerged. Here, Galluzzi and colleagues discuss the immune parameters that may predict the therapeutic response of patients to chemotherapeutics, and review the mechanisms by which current antineoplastic agents activate the immune system against cancer.
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anticancer effects of imatinib via Immunostimulation
Nature Medicine, 2011Co-Authors: Laurence Zitvogel, Guido KroemerAbstract:Imatinib represents the quintessential example of a targeted anticancer agent that directly suppresses the activation of oncogenic tyrosine kinases. Surprisingly, in the context of gastrointestinal stromal tumors (GISTs), the therapeutic effect of imatinib crucially depends on the reactivation of an anticancer immune response (pages 1094–1100 ).
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anticancer immunochemotherapy using adjuvants with direct cytotoxic effects
Journal of Clinical Investigation, 2009Co-Authors: Laurence Zitvogel, Guido KroemerAbstract:Conventional chemotherapeutics may induce immunogenic cancer cell death or stimulate immune effectors via so-called off-target effects. The study by Besch et al. in this issue of the JCI now demonstrates that agents designed to stimulate the innate immune system by activating intracellular pattern recognition receptors can kill cancer cells in a direct, cell-autonomous fashion (see the related article beginning on page 2399). The authors show that ligation of viral RNA sensors, such as RIG-I or MDA-5, by viral RNA mimetics triggers mitochondrial apoptosis in human melanoma cells in an IFN-independent fashion. The data suggest that tumor cell killing and Immunostimulation may synergize for optimal anticancer immunochemotherapy.
