Transplant Trial Watch.
Ontology highlight
ABSTRACT:
SUBMITTER: O'Callaghan JM
PROVIDER: S-EPMC9302583 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:During the last two decades, a number of approaches for the activation of the immune system against cancer has been developed. These include highly specific interventions, such as monoclonal antibodies, vaccines and cell-based therapies, as well as relatively unselective strategies, such as the systemic administration of adjuvants and immunomodulatory cytokines. Cytokines constitute a huge group of proteins that, taken together, regulate not only virtually all the aspects of innate and cognate immunity, but also several other cellular and organismal functions. Cytokines operate via specific transmembrane receptors that are expressed on the plasma membrane of target cells and, depending on multiple variables, can engage autocrine, paracrine or endocrine signaling pathways. The most appropriate term for defining the cytokine network is "pleiotropic": cytokines are produced by - and operate on - multiple, often overlapping, cell types, triggering context-depend biological outcomes as diverse as cell proliferation, chemotaxis, differentiation, inflammation, elimination of pathogens and cell death. Moreover, cytokines often induce the release of additional cytokines, thereby engaging self-amplificatory or self-inhibitory signaling cascades. In this Trial Watch, we will summarize the biological properties of cytokines and discuss the progress of ongoing clinical studies evaluating their safety and efficacy as immunomodulatory agents against cancer.
| S-EPMC3382908 | biostudies-literature
Project description:During the past two decades, the notion that cancer would merely constitute a cell-intrinsic disease has gradually been complemented by a model postulating that the immune system plays a relevant role during all stages of oncogenesis and tumor progression. Along with this conceptual shift, several strategies have been devised to stimulate tumor-specific immune responses, including relatively unselective approaches such as the systemic administration of adjuvants or immunomodulatory cytokines. One year ago, in the July issue of OncoImmunology, we described the main biological features of this large group of proteins and discussed the progress of ongoing clinical studies evaluating their safety and therapeutic potential in cancer patients. Here, we summarize the latest developments in this area of clinical research, focusing on high impact studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate which cytokines can be employed as safe and efficient immunostimulatory interventions against cancer.
| S-EPMC3782010 | biostudies-literature
Project description:Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and ?-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in cancer patients.
| S-EPMC3850274 | biostudies-literature
Project description:While chemotherapy and radiotherapy remain the first-line approaches for the management of most unresectable tumors, immunotherapy has emerged in the past two decades as a game-changing treatment, notably with the clinical success of immune checkpoint inhibitors. Immunotherapies aim at (re)activating anticancer immune responses which occur in two main steps: (1) the activation and expansion of tumor-specific T cells following cross-presentation of tumor antigens by specialized myeloid cells (priming phase); and (2) the immunological clearance of malignant cells by these antitumor T lymphocytes (effector phase). Therapeutic vaccines, adjuvants, monoclonal antibodies, cytokines, immunogenic cell death-inducing agents including oncolytic viruses, anthracycline-based chemotherapy and radiotherapy, as well as adoptive cell transfer, all act at different levels of this cascade to (re)instate cancer immunosurveillance. Intratumoral delivery of these immunotherapeutics is being tested in clinical trials to promote superior antitumor immune activity in the context of limited systemic toxicity.
| S-EPMC8526014 | biostudies-literature
Project description:Lenalidomide is a synthetic derivative of thalidomide currently approved by the US Food and Drug Administration for use in patients affected by multiple myeloma (in combination with dexamethasone) and low or intermediate-1 risk myelodysplastic syndromes that harbor 5q cytogenetic abnormalities. For illustrative purposes, the mechanism of action of lenalidomide can be subdivided into a cancer cell-intrinsic, a stromal, and an immunological component. Indeed, lenalidomide not only exerts direct cell cycle-arresting and pro-apoptotic effects on malignant cells, but also interferes with their physical and functional interaction with the tumor microenvironment and mediates a robust, pleiotropic immunostimulatory activity. In particular, lenalidomide has been shown to stimulate the cytotoxic functions of T lymphocytes and natural killer cells, to limit the immunosuppressive impact of regulatory T cells, and to modulate the secretion of a wide range of cytokines, including tumor necrosis factor ?, interferon ? as well as interleukin (IL)-6, IL-10, and IL-12. Throughout the last decade, the antineoplastic and immunostimulatory potential of lenalidomide has been investigated in patients affected by a wide variety of hematological and solid malignancies. Here, we discuss the results of these studies and review the status of clinical trials currently assessing the safety and efficacy of this potent immunomodulatory drug in oncological indications.
| S-EPMC3897503 | biostudies-literature
Project description:Malignant cells express antigens that can be harnessed to elicit anticancer immune responses. One approach to achieve such goal consists in the administration of tumor-associated antigens (TAAs) or peptides thereof as recombinant proteins in the presence of adequate adjuvants. Throughout the past decade, peptide vaccines have been shown to mediate antineoplastic effects in various murine tumor models, especially when administered in the context of potent immunostimulatory regimens. In spite of multiple limitations, first of all the fact that anticancer vaccines are often employed as therapeutic (rather than prophylactic) agents, this immunotherapeutic paradigm has been intensively investigated in clinical scenarios, with promising results. Currently, both experimentalists and clinicians are focusing their efforts on the identification of so-called tumor rejection antigens, i.e., TAAs that can elicit an immune response leading to disease eradication, as well as to combinatorial immunostimulatory interventions with superior adjuvant activity in patients. Here, we summarize the latest advances in the development of peptide vaccines for cancer therapy.
| S-EPMC4485775 | biostudies-literature