1,721,372 research outputs found

    Therapeutic idiotype vaccines in B lymphoproliferative diseases

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    The recognition of the surface immunoglobulin protein of the tumour B cells as a specific tumour antigen has prompted the development of vaccination strategies aimed at the induction of humoral and cellular antitumour responses. Results obtained in preclinical models of B lymphoproliferative diseases, as well as in initial clinical trials, have shown the immunogenic potential of the idiotype (Id) when administered in association with proper adjuvants. The definitive evidence for clinical efficacy of this therapeutic approach awaits ongoing randomised Phase III studies. Research efforts at present include identification of new vaccination settings to improve the clinical benefit of vaccine treatment, the establishment of more convenient methods to produce individual Id vaccines and the development of new strategies of vaccination, including genetic vaccination

    Conductive and flexible materials containing graphene-DNA hybrids for cell culture applications

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    Multifunctional materials designed by integrating a nano-hybrid component with bioactive and electrically conductive properties in a polymeric support matrix have many attractive features for applications in the biomedical and biotechnology fields. For example, it is well known that cells sense the stiffness of their microenvironment, and they can regulate their shape and proliferation according to the rigidity of the underlying substrate. Moreover, flexible substrates that are also electrically conductive can be an ideal tool in applications involving electro-responsive cells, such as the neuronal cells. In previous work from our group it was established that nanostructured films made by DNA-solubilized carbon nanotubes, retain their electrical conductivity, as indicated by atomic force microscopy experiments combined with electrical measurements on the nanoscale level. Here, we use a similar procedure to solubilize graphene nanoplatelets in DNA solutions and then embed the self-assembled hybrid in a flexible polymer matrix based on silicone polymers

    Cancer immunotherapy with chemoattractant peptides

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    The chemokine/chemokine receptor network is an essential part of an intricate system of immunosurveillance and homeostasis, it promotes or suppresses neovascularization, affects and regulates directly or indirectly growth and metastasis of malignant cells. Numerous studies have been conducted to harness this network as therapeutic agents for cancer to redress the chemokine balance and control angiogenesis and tumour growth and metastasis. Second generation of immunotherapeutics and chemoattractant-based vaccines use chemokines and chemoattractant peptides to elicit antitumor immunity by a specific targeting and modulating subsets of effector leukocytes, including professional antigen presenting cells

    CAR-modified Cellular Therapies in Chronic Lymphocytic Leukemia: Is the Uphill Road Getting Less Steep?

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    The clinical development of chimeric antigen receptor (CAR) T-cell therapy has been more challenging for chronic lymphocytic leukemia (CLL) compared to other settings. One of the main reasons is the CLL-associated state of immune dysfunction that specifically involves patient-derived T cells. Here, we provide an overview of the clinical results obtained with CAR T-cell therapy in CLL, describing the identified immunologic reasons for the inferior efficacy. Novel CAR T-cell formulations, such as lisocabtagene maraleucel, administered alone or in combination with the Bruton tyrosine kinase inhibitor ibrutinib, are currently under investigation. These approaches are based on the rationale that improving the quality of the T-cell source and of the CAR T-cell product may deliver a more functional therapeutic weapon. Further strategies to boost the efficacy of CAR T cells should rely not only on the production of CAR T cells with an improved cellular composition but also on additional changes. Such alterations could include (1) the coadministration of immunomodulatory agents capable of counteracting CLL-related immunological alterations, (2) the design of improved CAR constructs (such as third- and fourth-generation CARs), (3) the incorporation into the manufacturing process of immunomodulatory compounds overcoming the T-cell defects, and (4) the use of allogeneic CAR T cells or alternative CAR-modified cellular vectors. These strategies may allow to develop more effective CAR-modified cellular therapies capable of counteracting the more aggressive and still incurable forms of CLL

    Vγ9Vδ2 T cell-based immunotherapy in hematological malignancies: from bench to bedside

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    Many hematological malignancies consist of tumor cells that are spontaneously recognized and killed by Vγ9Vδ2 T cells. These tumor cells generate high amounts of intracellular phosphorylated metabolites mimicking the natural ligands and display a wide range of stress-induced self-ligands that are recognized by Vγ9Vδ2 T cells via TCR-dependent and TCR-independent mechanisms. The intrinsic features of Vγ9Vδ2 T cells and that of tumor cells of hematological origin constitute an ideal combination from which to develop Vγ9Vδ2 T cell-based immune interventions. In this review, we will discuss the rationale, preclinical and clinical data in favor of this therapeutic strategy and the future perspectives of its development

    Nanomaterial-based biosensors for a real-time detection of biological damage by UV light

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    In this work, the design and fabrication of a miniaturized and light-weight biosensor that can be used to monitor the biological effects of hostile ultraviolet radiation in earth and space are presented. The biosensor is generated by embedding a sensitive element to UV radiation, DNA, in a hybrid carbon-based nanomaterial. In particular, we present results on the fabrication and characterization of hybrid nanostructured films containing graphene nanoplatelets (GNPs) and double-stranded DNA for the in situ and real-time detection of UV radiation damaging effects from the changes of the film electrical properties induced by exposure to UV-C radiation. The biosensor is realized by the deposition of the sensitive unit GNP/DNA on a supporting substrate made of flexible polymers or glass

    Immunotherapeutic strategies in chronic lymphocytic leukemia: advances and challenges

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    Immune-based therapeutic strategies have drastically changed the landscape of hematological disorders, as they have introduced the concept of boosting immune responses against tumor cells. Anti-CD20 monoclonal antibodies have been the first form of immunotherapy successfully applied in the treatment of CLL, in the context of chemoimmunotherapy regimens. Since then, several immunotherapeutic approaches have been studied in CLL settings, with the aim of exploiting or eliciting anti-tumor immune responses against leukemia cells. Unfortunately, despite initial promising data, results from pilot clinical studies have not shown optimal results in terms of disease control - especially when immunotherapy was used individually - largely due to CLL-related immune dysfunctions hampering the achievement of effective anti-tumor responses. The growing understanding of the complex interactions between immune cells and the tumor cells has paved the way for the development of new combined approaches that rely on the synergism between novel agents and immunotherapy. In this review, we provide an overview of the most successful and promising immunotherapeutic modalities in CLL, including both antibody-based therapy (i.e. monoclonal antibodies, bispecific antibodies, bi- or tri- specific killer engagers) and adoptive cellular therapy (i.e. CAR T cells and NK cells). We also provide examples of successful new combination strategies and some insights on future perspectives
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