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1.
J Transl Med ; 20(1): 391, 2022 09 04.
Article in English | MEDLINE | ID: covidwho-2009424

ABSTRACT

Advances in immune checkpoint and combination therapy have led to improvement in overall survival for patients with advanced melanoma. Improved understanding of the tumor, tumor microenvironment and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. Combination modalities with other immunotherapy agents, chemotherapy, radiotherapy, electrochemotherapy are also being explored to overcome resistance and to potentiate the immune response. In addition, novel approaches such as adoptive cell therapy, oncogenic viruses, vaccines and different strategies of drug administration including sequential, or combination treatment are being tested. Despite the progress in diagnosis of melanocytic lesions, correct classification of patients, selection of appropriate adjuvant and systemic theràapies, and prediction of response to therapy remain real challenges in melanoma. Improved understanding of the tumor microenvironment, tumor immunity and response to therapy has prompted extensive translational and clinical research in melanoma. There is a growing evidence that genomic and immune features of pre-treatment tumor biopsies may correlate with response in patients with melanoma and other cancers, but they have yet to be fully characterized and implemented clinically. Development of novel biomarker platforms may help to improve diagnostics and predictive accuracy for selection of patients for specific treatment. Overall, the future research efforts in melanoma therapeutics and translational research should focus on several aspects including: (a) developing robust biomarkers to predict efficacy of therapeutic modalities to guide clinical decision-making and optimize treatment regimens, (b) identifying mechanisms of therapeutic resistance to immune checkpoint inhibitors that are potentially actionable, (c) identifying biomarkers to predict therapy-induced adverse events, and (d) studying mechanism of actions of therapeutic agents and developing algorithms to optimize combination treatments. During the Melanoma Bridge meeting (December 2nd-4th, 2021, Naples, Italy) discussions focused on the currently approved systemic and local therapies for advanced melanoma and discussed novel biomarker strategies and advances in precision medicine as well as the impact of COVID-19 pandemic on management of melanoma patients.


Subject(s)
COVID-19 , Melanoma , Biomarkers , Humans , Immunotherapy/methods , Italy , Melanoma/genetics , Pandemics , Tumor Microenvironment
2.
J Immunother Cancer ; 10(6)2022 06.
Article in English | MEDLINE | ID: covidwho-2009227

ABSTRACT

Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous neuroendocrine carcinoma. The MCC incidence rate has rapidly grown over the last years, with Italy showing the highest increase among European countries. This malignancy has been the focus of active scientific research over the last years, focusing mainly on pathogenesis, new therapeutic trials and diagnosis. A national expert board developed 28 consensus statements that delineated the evolution of disease management and highlighted the paradigm shift towards the use of immunological strategies, which were then presented to a national MCC specialists panel for review. Sixty-five panelists answered both rounds of the questionnaire. The statements were divided into five areas: a high level of agreement was reached in the area of guidelines and multidisciplinary management, even if in real life the multidisciplinary team was not always represented by all the specialists. In the diagnostic pathway area, imaging played a crucial role in diagnosis and initial staging, planning for surgery or radiation therapy, assessment of treatment response and surveillance of recurrence and metastases. Concerning diagnosis, the usefulness of Merkel cell polyomavirus is recognized, but the agreement and consensus regarding the need for cytokeratin evaluation appears greater. Regarding the areas of clinical management and follow-up, patients with MCC require customized treatment. There was a wide dispersion of results and the suggestion to increase awareness about the adjuvant radiation therapy. The panelists unanimously agreed that the information concerning avelumab provided by the JAVELIN Merkel 200 study is adequate and reliable and that the expanded access program data could have concrete clinical implications. An immunocompromised patient with advanced MCC can be treated with immunotherapy after multidisciplinary risk/benefit assessment, as evidenced by real-world analysis and highlighted in the guidelines. A very high consensus regarding the addition of radiotherapy to treat the ongoing focal progression of immunotherapy was observed. This paper emphasizes the importance of collaboration and communication among the interprofessional team members and encourages managing patients with MCC within dedicated multidisciplinary teams. New insights in the treatment of this challenging cancer needs the contribution of many and different experts.


Subject(s)
Carcinoma, Merkel Cell , Merkel cell polyomavirus , Skin Neoplasms , Carcinoma, Merkel Cell/diagnosis , Carcinoma, Merkel Cell/pathology , Carcinoma, Merkel Cell/therapy , Humans , Immunotherapy/methods , Italy , Skin Neoplasms/drug therapy , Skin Neoplasms/therapy
6.
Proc Natl Acad Sci U S A ; 119(11): e2122954119, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1721790

ABSTRACT

SignificanceSARS-CoV-2 continues to evolve through emerging variants, more frequently observed with higher transmissibility. Despite the wide application of vaccines and antibodies, the selection pressure on the Spike protein may lead to further evolution of variants that include mutations that can evade immune response. To catch up with the virus's evolution, we introduced a deep learning approach to redesign the complementarity-determining regions (CDRs) to target multiple virus variants and obtained an antibody that broadly neutralizes SARS-CoV-2 variants.


Subject(s)
Broadly Neutralizing Antibodies/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/pharmacology , COVID-19 Vaccines/immunology , Complementarity Determining Regions , Deep Learning , Epitopes/immunology , Humans , Immunotherapy/methods , Neutralization Tests/methods , Protein Domains , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
7.
Int Immunopharmacol ; 107: 108655, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1699273

ABSTRACT

Multiple efforts are currently underway to control and treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) worldwide. Despite all efforts, the virus that emerged in Wuhan city has rapidly spread globally and led to a public health emergency of international concern (PHEIC) due to the lack of approved antiviral therapy. Nevertheless, SARS-CoV-2 has had a significant influence on the evolution of cellular therapeutic approaches. Adoptive immune cell therapy is innovative and offers either promising prophylactic or therapy for patients with moderate-to-severe COVID-19. This approach is aimed at developing safety and providing secure and effective therapy in combination with standard therapy for all COVID-19 infected individuals. Based on the effective results of previous studies on both inflammatory and autoimmune diseases, various immune cell therapies against COVID-19 have been reviewed and discussed. It must be considered that the application of cell therapy for treatment and to eliminate infected respiratory cells could result in excessive inflammation, so this treatment must be used in combination with other treatments, despite its many beneficial efforts.


Subject(s)
COVID-19 , COVID-19/therapy , Humans , Immunologic Factors , Immunotherapy/methods , Inflammation , SARS-CoV-2
9.
ACS Appl Mater Interfaces ; 14(3): 4456-4468, 2022 Jan 26.
Article in English | MEDLINE | ID: covidwho-1619771

ABSTRACT

Coronavirus represents an inspiring model for designing drug delivery systems due to its unique infection machinery mechanism. Herein, we have developed a biomimetic viruslike nanocomplex, termed SDN, for improving cancer theranostics. SDN has a unique core-shell structure consisting of photosensitizer chlorin e6 (Ce6)-loaded nanostructured lipid carrier (CeNLC) (virus core)@poly(allylamine hydrochloride)-functionalized MnO2 nanoparticles (virus spike), generating a virus-mimicking nanocomplex. SDN not only prompted cellular uptake through rough-surface-mediated endocytosis but also achieved mitochondrial accumulation by the interaction of cationic spikes and the anionic mitochondrial surface, leading to mitochondria-specific photodynamic therapy. Meanwhile, SDN could even mediate oxygen generation to relieve tumor hypoxia and, consequently, improve macrophage-associated anticancer immune response. Importantly, SDN served as a robust magnetic resonance imaging (MRI) contrast agent due to the fast release of Mn2+ in the presence of intracellular redox components. We identified that SDN selectively accumulated in tumors and released Mn2+ to generate a 5.71-fold higher T1-MRI signal, allowing for effectively detecting suspected tumors. Particularly, SDN induced synergistic immunophotodynamic effects to eliminate malignant tumors with minimal adverse effects. Therefore, we present a novel biomimetic strategy for improving targeted theranostics, which has a wide range of potential biomedical applications.


Subject(s)
Drug Delivery Systems , Nanoparticles/chemistry , Neoplasms/therapy , SARS-CoV-2/chemistry , Bionics/methods , Cell Line, Tumor , Chlorophyllides/chemistry , Chlorophyllides/pharmacology , Contrast Media/chemistry , Contrast Media/pharmacology , Humans , Immunotherapy/methods , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Neoplasms/immunology , Oxides/chemistry , Oxides/pharmacology , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Polyamines/chemistry , Polyamines/pharmacology
10.
Int J Biol Sci ; 18(1): 386-408, 2022.
Article in English | MEDLINE | ID: covidwho-1607858

ABSTRACT

Responding to the coronavirus disease 2019 (COVID-19) pandemic has been an unexpected and unprecedented global challenge for humanity in this century. During this crisis, specialists from the laboratories and frontline clinical personnel have made great efforts to prevent and treat COVID-19 by revealing the molecular biological characteristics and epidemic characteristics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, SARS-CoV-2 has severe consequences for public health, including human respiratory system, immune system, blood circulation system, nervous system, motor system, urinary system, reproductive system and digestive system. In the review, we summarize the physiological and pathological damage of SARS-CoV-2 to these systems and its molecular mechanisms followed by clinical manifestation. Concurrently, the prevention and treatment strategies of COVID-19 will be discussed in preclinical and clinical studies. With constantly unfolding and expanding scientific understanding about COVID-19, the updated information can help applied researchers understand the disease to build potential antiviral drugs or vaccines, and formulate creative therapeutic ideas for combating COVID-19 at speed.


Subject(s)
COVID-19/pathology , COVID-19/therapy , Immunotherapy/methods , SARS-CoV-2 , Animals , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19 Vaccines , Cytokines/metabolism , Female , Humans , Immune System , Immunity, Innate , Immunologic Memory , Male , Mice
11.
Adv Sci (Weinh) ; 8(24): e2102330, 2021 12.
Article in English | MEDLINE | ID: covidwho-1599388

ABSTRACT

Immune modulation is one of the most effective approaches in the therapy of complex diseases, including public health emergency. However, most immune therapeutics such as drugs, vaccines, and cellular therapy suffer from the limitations of poor efficacy and adverse side effects. Fortunately, cell membrane-derived nanoparticles (CMDNs) have superior compatibility with other therapeutics and offer new opportunities to push the limits of current treatments in immune modulation. As the interface between cells and outer surroundings, cell membrane contains components which instruct intercellular communication and the plasticity of cytomembrane has significantly potentiated CMDNs to leverage our immune system. Therefore, cell membranes employed in immunomodulatory CMDNs have gradually shifted from natural to engineered. In this review, unique properties of immunomodulatory CMDNs and engineering strategies of emerging CMDNs for immune modulation, with an emphasis on the design logic are summarized. Further, this review points out some pressing problems to be solved during clinical translation and put forward some suggestions on the prospect of immunoregulatory CMDNs. It is anticipated that this review can provide new insights on the design of immunoregulatory CMDNs and expand their potentiation in the precise control of the dysregulated immune system.


Subject(s)
Cell Membrane/immunology , Cell- and Tissue-Based Therapy/methods , Immunotherapy/methods , Nanoparticles/therapeutic use , Animals , Disease Models, Animal , Humans , Immunomodulation , Mice
12.
Int J Mol Sci ; 23(1)2021 Dec 31.
Article in English | MEDLINE | ID: covidwho-1580694

ABSTRACT

Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments.


Subject(s)
Lung Diseases/genetics , Lung Diseases/immunology , Telomere Shortening/immunology , Animals , COVID-19/genetics , COVID-19/immunology , Cellular Senescence/genetics , Genetic Therapy/methods , Humans , Immunotherapy/methods , Lung Diseases/drug therapy
13.
Adv Drug Deliv Rev ; 181: 114081, 2022 02.
Article in English | MEDLINE | ID: covidwho-1568454

ABSTRACT

With numerous recent advances, the field of therapeutic nucleic acid nanotechnology is now poised for clinical translation supported by several examples of FDA-approved nucleic acid nanoformulations including two recent mRNA-based COVID-19 vaccines. Within this rapidly growing field, a new subclass of nucleic acid therapeutics called nucleic acid nanoparticles (NANPs) has emerged in recent years, which offers several unique properties distinguishing it from traditional therapeutic nucleic acids. Key unique aspects of NANPs include their well-defined 3D structure, their tunable multivalent architectures, and their ability to incorporate conditional activations of therapeutic targeting and release functions that enable diagnosis and therapy of cancer, regulation of blood coagulation disorders, as well as the development of novel vaccines, immunotherapies, and gene therapies. However, non-consolidated research developments of this highly interdisciplinary field create crucial barriers that must be overcome in order to impact a broader range of clinical indications. Forming a consortium framework for nucleic acid nanotechnology would prioritize and consolidate translational efforts, offer several unifying solutions to expedite their transition from bench-to-bedside, and potentially decrease the socio-economic burden on patients for a range of conditions. Herein, we review the unique properties of NANPs in the context of therapeutic applications and discuss their associated translational challenges.


Subject(s)
Nanoparticles/chemistry , Nanoparticles/therapeutic use , Nucleic Acids/chemistry , Nucleic Acids/therapeutic use , Animals , COVID-19/drug therapy , COVID-19/immunology , COVID-19 Vaccines/immunology , Drug Delivery Systems/methods , Humans , Immunotherapy/methods , Nanotechnology/methods , SARS-CoV-2/drug effects
14.
Biomed Pharmacother ; 145: 112385, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1565522

ABSTRACT

Chemically modified mRNA represents a unique, efficient, and straightforward approach to produce a class of biopharmaceutical agents. It has been already approved as a vaccination-based method for targeting SARS-CoV-2 virus. The COVID-19 pandemic has highlighted the prospect of synthetic modified mRNA to efficiently and safely combat various diseases. Recently, various optimization advances have been adopted to overcome the limitations associated with conventional gene therapeutics leading to wide-ranging applications in different disease conditions. This review sheds light on emerging directions of chemically modified mRNAs to prevent and treat widespread chronic diseases, including metabolic disorders, cancer vaccination and immunotherapy, musculoskeletal disorders, respiratory conditions, cardiovascular diseases, and liver diseases.


Subject(s)
COVID-19/prevention & control , Chronic Disease/prevention & control , Chronic Disease/therapy , Genetic Therapy/methods , Immunotherapy/methods , Pandemics/prevention & control , RNA, Messenger/chemistry , SARS-CoV-2/immunology , Vaccines, Synthetic , Biological Availability , Drug Carriers , Forecasting , Gene Transfer Techniques , Genetic Vectors/administration & dosage , Genetic Vectors/therapeutic use , Humans , Immunotherapy, Active , RNA Stability , RNA, Messenger/administration & dosage , RNA, Messenger/immunology , RNA, Messenger/therapeutic use , SARS-CoV-2/genetics , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , /immunology
15.
Front Biosci (Landmark Ed) ; 26(11): 1274-1285, 2021 11 30.
Article in English | MEDLINE | ID: covidwho-1552203

ABSTRACT

The COVID-19 pandemic is not just a medical and epidemiological problem. In fact, its impact concerns numerous aspects of human life (such as social and the political-economic dimension). This review aims at highlighting some crucial and neglected aspects of the pandemic in order to include them into a more general framework for the understanding of the phenomenon. Accordingly, it is structured as follows. First, after e brief recap of COVID-19 onset, it is argued the so-called proximate causes of the pandemic, i.e., the mechanisms by which viruses infect their hosts and the patterns of spread of the resulting pathologies, are not enough for a more adequate understanding of it. Second, it is shown how possible solutions to the risk of an upcoming pandemic involve studying the ultimate causes of this phenomenon. This means understanding not only how COVID-19 has become a global issue but also why it was possible for this to happen. Next, it is argued that is urgent to go to the root of the possible conditions: thus looking at the ecological dimension of diseases, the role of microorganisms in evolution, up to rethinking the organization of health systems. Third, to keep these very different perspectives together entails the study of COVID-19 from the point of view of the relationships between biological entities in a purely systemic dimension. Fourth, special attention is given to the symbiotic perspective offered by the study of the microbiota. It is argued how this perspective on microbiota provides an innovative interpretative lens with which to analyze various aspects (from the immunological to the ecosystemic one) of the pandemic. In conclusion, it is claimed that this field of study could perhaps offer not only elements that will be useful to make the treatment and containment strategies of the pandemic effective in its mechanisms, but also may suggest innovative elements for the solutions about the deep reasons that have made COVID-19 a global issue.


Subject(s)
COVID-19/prevention & control , Immunotherapy/methods , COVID-19/immunology , COVID-19/virology , Humans , SARS-CoV-2/isolation & purification
16.
Front Immunol ; 12: 765349, 2021.
Article in English | MEDLINE | ID: covidwho-1551508

ABSTRACT

The development of vaccines against infectious diseases has helped us battle the greatest threat to public health. With the emergence of novel viruses, targeted immunotherapeutics ranging from informed vaccine development to personalized medicine may be the very thing that separates us between life and death. Late in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), made a remarkable entrance to human civilization, being one of many to cross the species barrier. This review discusses the important aspects of COVID-19, providing a brief overview of our current understanding of dysregulated immune responses developed using various experimental models, a brief outline of experimental models of COVID-19 and more importantly, the rapid development of vaccines against COVID-19.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/pathology , COVID-19/prevention & control , SARS-CoV-2/immunology , Adaptive Immunity/immunology , Animals , COVID-19/therapy , Cytokine Release Syndrome/pathology , Cytokines/biosynthesis , Cytokines/immunology , Disease Models, Animal , Humans , Immunotherapy/methods , Myeloid Cells/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccination
17.
Med Sci Monit ; 27: e934267, 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1534578

ABSTRACT

BACKGROUND The use of monoclonal antibodies therapy (MAT) in early mild to moderate Coronavirus disease 2019 (COVID-19) has gained importance in recent times. However, there is limited information on the safety and efficacy of MAT in treating COVID-19 in patients with underlying rheumatologic diseases. Patients with rheumatologic diseases are usually on long-term corticosteroids and immunosuppressive therapy, which increases their risk for progressing to more severe forms of COVID-19. We report a case series of 4 patients with rheumatologic diseases who were treated with MAT for COVID-19. MATERIAL AND METHODS A retrospective observational study was conducted in our institution on patients with underlying rheumatological disorders who received MAT as per the EUA protocol of the FDA. RESULTS Two of the 4 patients were on immunosuppresive therapy at the time of receiving MAT. They recovered from COVID-19 without any adverse outcomes. No flare of underlying rheumatologic disease was noted. CONCLUSIONS MAT was observed to be a safe and effective therapy in 4 patients with rheumatological illnesses and COVID-19 treated at our hospital.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Arthritis, Rheumatoid/epidemiology , COVID-19 , Immunotherapy/methods , SARS-CoV-2/immunology , Aged , COVID-19/drug therapy , COVID-19/epidemiology , Comorbidity , Female , Humans , Middle Aged , Treatment Outcome
18.
Br J Cancer ; 126(1): 1-3, 2022 01.
Article in English | MEDLINE | ID: covidwho-1526066

ABSTRACT

The combination of COVID-19 vaccination with immunotherapy by checkpoint inhibitors in cancer patients could intensify immunological stimulation with potential reciprocal benefits. Here, we examine more closely the possible adverse events that can arise in each treatment modality. Our conclusion is that caution should be exercised when combining both treatments.


Subject(s)
/adverse effects , COVID-19/prevention & control , Immune Checkpoint Inhibitors/adverse effects , Immunotherapy/adverse effects , Neoplasms/therapy , /administration & dosage , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Combined Modality Therapy/adverse effects , Cytokine Release Syndrome/etiology , Drug Interactions , Humans , Immune Checkpoint Inhibitors/administration & dosage , Immunotherapy/methods , Neoplasms/immunology
19.
Nat Med ; 27(11): 1990-2001, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526094

ABSTRACT

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.


Subject(s)
COVID-19 Vaccines/therapeutic use , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/analysis , Antibodies, Viral/blood , Antigens, CD20/immunology , COVID-19/prevention & control , Case-Control Studies , Chlorocebus aethiops , HEK293 Cells , Humans , Immunity, Cellular , Immunity, Humoral/drug effects , Immunity, Humoral/physiology , Immunotherapy/methods , Longitudinal Studies , Multiple Sclerosis/blood , RNA, Messenger/immunology , RNA, Viral/immunology , Rituximab/pharmacology , Rituximab/therapeutic use , SARS-CoV-2/genetics , Vaccination , Vero Cells
20.
Theranostics ; 11(20): 10012-10029, 2021.
Article in English | MEDLINE | ID: covidwho-1512995

ABSTRACT

Various living organisms have proven to influence human health significantly, either in a commensal or pathogenic manner. Harnessing the creatures may remarkably improve human healthcare and cure the intractable illness that is challenged using traditional drugs or surgical approaches. However, issues including limited biocompatibility, poor biosafety, inconvenience for personal handling, and low patient compliance greatly hinder the biomedical and clinical applications of living organisms when adopting them for disease treatment. Microneedle arrays (MNAs), emerging as a promising candidate of biomedical devices with the functional diversity and minimal invasion, have exhibited great potential in the treatment of a broad spectrum of diseases, which is expected to improve organism-based therapies. In this review, we systemically summarize the technologies employed for the integration of MNAs with specific living organisms including diverse viruses, bacteria, mammal cells and so on. Moreover, their applications such as vaccination, anti-infection, tumor therapy and tissue repairing are well illustrated. Challenges faced by current strategies, and the perspectives of integrating more living organisms, adopting smarter materials, and developing more advanced technologies in MNAs for future personalized and point-of-care medicine, are also discussed. It is believed that the combination of living organisms with functional MNAs would hold great promise in the near future due to the advantages of both biological and artificial species.


Subject(s)
Biological Therapy/methods , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Administration, Cutaneous , Bacteria , Biological Therapy/trends , Cells , Immunotherapy/methods , Immunotherapy/trends , Needles , Skin/drug effects , Vaccination/methods , Vaccination/trends , Viruses
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