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RISS 인기검색어
- 검색키워드
- 저자 : Diederich, (검색결과 38 건)
- 무료
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Natural compound inducers of immunogenic cell death
Marc Diederich 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.7
Accumulating evidence shows that the anticancerpotential of the immune response that can be activatedby modulation of the immunogenicity of dyingcancer cells. This regulated cell death process is calledimmunogenic cell death (ICD) and constitutes a newinnovating anti-cancer strategy with immune-modulatorypotential thanks to the release of damage-associatedmolecular patterns (DAMPs). Some conventional clinically-used chemotherapeutic drugs, as well as preclinically-investigated compounds of natural origins such asanthracyclines, microtubule-destabilizing agents, cardiacglycosides or hypericin derivatives, possess such animmune-stimulatory function by triggering ICD. Here, wediscuss the effects of ICD inducers on the release ofDAMPs and the activation of corresponding signalingpathways triggering immune recognition. We will discusspotential strategies allowing to overcome resistancemechanisms associated with this treatment approach aswell as co-treatment strategies to overcome the immunosuppressivemicroenvironment. We will highlight thepotential role of metronomic immune modulation as wellas targeted delivery of ICD-inducing compounds withnanoparticles or liposomal formulations to improving theimmunogenicity of ICD inducers aiming at long-termclinical benefits.
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Bispecific Antibodies: An Innovative Arsenal to Hunt, Grab and Destroy Cancer Cells
Dicato, Mario,Diederich, Marc Bentham Science 2015 CURRENT PHARMACEUTICAL BIOTECHNOLOGY Vol.16 No.8
<P>Targeted cellular immunotherapy with bifunctional antibodies (bsAbs) has emerged as a promising therapeutic approach for cancer over the last two decades. Progress in antibody engineering has led to the generation of many different types of antibody-derived entities that display at least two binding specificities. Most bsAbs consist of large IgG-like proteins with multiple antigen-binding regions containing Fc parts or smaller entities without Fc. BsAbs have the potential to engage effector cells of the immune system, thereby overcoming some of the immune response escape mechanisms of tumor cells. Preclinical and clinical trials of various bsAb constructs have demonstrated impressive results in terms of immune effector cell retargeting and induction of efficient anti-tumor responses. This review provides an overview of the established bsAbs focusing on improvements in format and design as well as the mechanisms of action of the most promising candidates and describes the results of the most recent clinical studies.</P>
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Stress-induced cellular responses in immunogenic cell death: Implications for cancer immunotherapy
Radogna, Flavia,Diederich, Marc Elsevier 2018 Biochemical pharmacology Vol.153 No.-
<P><B>Abstract</B></P> <P>Cancer is evading the host’s defense mechanisms leading to avoidance of immune destruction. During tumor progression, immune-evading cancer cells arise due to selective pressure from the hypoxic and nutrient-deprived microenvironment. Thus, therapies aiming at re-establishing immune destruction of pathological cells constitute innovating anti-cancer strategies. Accumulating evidence suggests that selected conventional chemotherapeutic drugs increase the immunogenicity of stressed and dying cancer cells by triggering a form of cell death called immunogenic cell death (ICD), which is characterized by the release of danger-associated molecular patterns (DAMPs). In this review, we summarize the effects of ICD inducers on DAMP signaling leading to adjuvanticity and antigenicity. We will discuss the associated stress response pathways that cause the release of DAMPs leading to improved immune recognition and their relevance in cancer immunotherapy. Our aim is to highlight the contribution of adaptive immunity to the long-term clinical benefits of anticancer treatments and the properties of immune memory that can protect cancer patients against relapse.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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Natural modulators of the hallmarks of immunogenic cell death
Radogna, Flavia,Dicato, Mario,Diederich, Marc Pergamon Press 2019 Biochemical pharmacology Vol.162 No.-
<P><B>Abstract</B></P> <P>Natural compounds act as immunoadjuvants as their therapeutic effects trigger cancer stress response and release of damage-associated molecular patterns (DAMPs). These reactions occur through an increase in the immunogenicity of cancer cells that undergo stress followed by immunogenic cell death (ICD). These processes result in a chemotherapeutic response with a potent immune-mediating reaction. Natural compounds that induce ICD may function as an interesting approach in converting cancer into its own vaccine. However, multiple parameters determine whether a compound can act as an ICD inducer, including the nature of the inducer, the <I>premortem</I> stress pathways, the cell death pathways, the intrinsic antigenicity of the cell, and the potency and availability of an immune cell response. Thus, the identification of hallmarks of ICD is important in determining the prognostic biomarkers for new therapeutic approaches and combination treatments.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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Natural scaffolds in anticancer therapy and precision medicine
Mazumder, Aloran,Cerella, Claudia,Diederich, Marc Elsevier 2018 BIOTECHNOLOGY ADVANCES Vol.36 No.6
<P>The diversity of natural compounds is essential for their mechanism of action. The source, structures and structure activity relationship of natural compounds contributed to the development of new classes of chemotherapy agents for over 40 years. The availability of combinatorial chemistry and high-throughput screening has fueled the challenge to identify novel compounds that mimic natures chemistry and to predict their macromolecular targets. Combining conventional and targeted therapies helped to successfully overcome drug resistance and prolong disease-free survival. Here, we aim to provide an overview of preclinical investigated natural compounds alone and in combination to further improve personalization of cancer treatment.</P>
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Plant-derived epigenetic modulators for cancer treatment and prevention
Schnekenburger, M.,Dicato, M.,Diederich, M. Pergamon Press ; Elsevier Science Ltd 2014 BIOTECHNOLOGY ADVANCES Vol.32 No.6
Carcinogenesis is a complex and multistep process that involves the accumulation of successive transformational events driven by genetic mutations and epigenetic alterations that affect major cellular processes and pathways such as proliferation, differentiation, invasion and survival. Massive deregulation of all components of the epigenetic machinery is a hallmark of cancer. These alterations affect normal gene regulation and impede normal cellular processes including cell cycle, DNA repair, cell growth, differentiation and apoptosis. Since epigenetic alterations appear early in cancer development and represent potentially initiating events during carcinogenesis, they are considered as promising targets for anti-cancer interventions by chemopreventive and chemotherapeutic strategies using epigenetically active agents. In this field, plant-derived compounds have shown promise. Here, we will give an overview of plant-derived compounds displaying anticancer properties that interfere with the epigenetic machinery.
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Natural Compounds as Regulators of the Cancer Cell Metabolism
Cerella, Claudia,Radogna, Flavia,Dicato, Mario,Diederich, Marc Hindawi Publishing Corporation 2013 International journal of cell biology Vol.2013 No.-
<P>Even though altered metabolism is an “old” physiological mechanism, only recently its targeting became a therapeutically interesting strategy and by now it is considered an emerging hallmark of cancer. Nevertheless, a very poor number of compounds are under investigation as potential modulators of cell metabolism. Candidate agents should display selectivity of action towards cancer cells without side effects. This ideal favorable profile would perfectly overlap the requisites of new anticancer therapies and chemopreventive strategies as well. Nature represents a still largely unexplored source of bioactive molecules with a therapeutic potential. Many of these compounds have already been characterized for their multiple anticancer activities. Many of them are absorbed with the diet and therefore possess a known profile in terms of tolerability and bioavailability compared to newly synthetized chemical compounds. The discovery of important cross-talks between mediators of the most therapeutically targeted aberrancies in cancer (i.e., cell proliferation, survival, and migration) and the metabolic machinery allows to predict the possibility that many anticancer activities ascribed to a number of natural compounds may be due, in part, to their ability of modulating metabolic pathways. In this review, we attempt an overview of what is currently known about the potential of natural compounds as modulators of cancer cell metabolism.</P>
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