Frontiers in immunology
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Frontiers in immunology · Jan 2020
ReviewA 21st Century Evil: Immunopathology and New Therapies of COVID-19.
Coronavirus Disease 2019 (COVID-19) has been classified as a global threat, affecting millions of people and killing thousands. It is caused by the SARS-CoV-2 virus, which emerged at the end of 2019 in Wuhan, China, quickly spreading worldwide. COVID-19 is a disease with symptoms that range from fever and breathing difficulty to acute respiratory distress and death, critically affecting older patients and people with previous comorbidities. ⋯ The immune system of infected patients has been demonstrated to suffer important alterations, such as lymphopenia, exhausted lymphocytes, excessive amounts of inflammatory monocytes and macrophages, especially in the lungs, and cytokine storms, which may contribute to its severity and difficulty of establishing an effective treatment. Even though no specific treatment is currently available, several studies have been investigating potential therapeutic strategies, including the use of previously approved drugs and immunotherapy. In this context, this review addresses the interaction between SARS-CoV-2 and the patient's host immune system during infection, in addition to discussing the main immunopathological mechanisms involved in the development of the disease and potential new therapeutic approaches.
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Frontiers in immunology · Jan 2020
ReviewHow to Combine the Two Landmark Treatment Methods-Allogeneic Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Together to Cure High-Risk B Cell Acute Lymphoblastic Leukemia?
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has made tremendous progress in the last few decades and is increasingly being used worldwide. The success of haploidentical HSCT has made it possible to have "a donor for everyone". Patients who received transplantation in remission may have a favorable outcome, while those who were transplanted in advanced stages of disease have a poor prognosis. ⋯ Therefore, combining these two approaches (allo-HSCT and CAR-T cell therapy) is an attractive area of research to further improve the prognosis of R/R B-ALL. In this review, we will discuss the current clinical practices of combining allo-HSCT with CAR-T cell therapy based on available data, including CAR-T cells as a bridge to allo-HSCT for R/R B-ALL and CAR-T cell infusion for post-transplant relapse. We will further explore not only other possible ways to combine the two approaches, including CAR-T cell therapy to clear minimal residual disease peri-transplantation and incorporation of CAR technology to treat graft-versus-host disease, but also the potential of CAR-T cells as a part of allo-HSCT.
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Frontiers in immunology · Jan 2020
ReviewBefriending the Hostile Tumor Microenvironment in CAR T-Cell Therapy.
T-cells genetically engineered to express a chimeric antigen receptor (CAR) have shown remarkable results in patients with B-cell malignancies, including B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and mantle cell lymphoma, with some promising efficacy in patients with multiple myeloma. However, the efficacy of CAR T-cell therapy is still hampered by local immunosuppression and significant toxicities, notably cytokine release syndrome (CRS) and neurotoxicity. The tumor microenvironment (TME) has been identified to play a major role in preventing durable responses to immunotherapy in both solid and hematologic malignancies, with this role exaggerated in solid tumors. ⋯ Herein, we discuss the mechanisms by which the TME antagonizes CAR T-cells and how innovative immunotherapy strategies are being developed to address this roadblock. Furthermore, we offer perspective on how these novel approaches may affect the risk of adverse events, in order to identify ways to overcome these barriers and expand the clinical benefits of this treatment modality in patients with diverse cancers. Precise immunomodulation to allow for improved tumor control while simultaneously mitigating the toxicities seen with current generation CAR T-cells is integral for the future application of more effective CAR T-cells against other malignancies.
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Frontiers in immunology · Jan 2020
ReviewAndrogen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung.
Androgens, the predominant male sex hormones, drive the development and maintenance of male characteristics by binding to androgen receptor (AR). As androgens are systemically distributed throughout the whole organism, they affect many tissues and cell types in addition to those in male sexual organs. It is now clear that the immune system is a target of androgen action. ⋯ We also discuss the therapeutic use of androgens and how circulating androgens correlate with lung disease. In addition to human studies, we also discuss how mouse models have helped to uncover the effect of androgens on monocytes and macrophages in lung disease. Although the role of estrogen and other female hormones has been broadly analyzed in the literature, we focus on the new perspectives of androgens as modulators of the immune system that target myeloid cells during lung inflammation.
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Frontiers in immunology · Jan 2020
ReviewStrategies for Targeting SARS CoV-2: Small Molecule Inhibitors-The Current Status.
Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease - 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. ⋯ Hence, the current interest is shifted toward the development of NSMIs, which includes natural antiviral phytochemicals and Nrf-2 activators to manage a SARS-CoV-2 infection. It is imperative to investigate the efficacy of existing antiviral phytochemicals and Nrf-2 activators to mitigate the SARS-CoV-2-mediated oxidative stress. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs.