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International Journal of Biological... 2019Cancer immunotherapy by chimeric antigen receptor-modified T (CAR-T) cells has shown exhilarative clinical efficacy for hematological malignancies. Recently two CAR-T... (Review)
Review
Cancer immunotherapy by chimeric antigen receptor-modified T (CAR-T) cells has shown exhilarative clinical efficacy for hematological malignancies. Recently two CAR-T cell based therapeutics, Kymriah (Tisagenlecleucel) and Yescarta (Axicabtagene ciloleucel) approved by US FDA (US Food and Drug Administration) are now used for treatment of B cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) respectively in the US. Despite the progresses made in treating hematological malignancies, challenges still remain for use of CAR-T cell therapy to treat solid tumors. In this landscape, most studies have primarily focused on improving CAR-T cells and overcoming the unfavorable effects of tumor microenvironment on solid tumors. To further understand the current status and trend for developing CAR-T cell based therapies for various solid tumors, this review emphasizes on CAR-T techniques, current obstacles, and strategies for application, as well as necessary companion diagnostics for treatment of solid tumors with CAR-T cells.
Topics: Cytokine Release Syndrome; Cytokines; Humans; Immunotherapy, Adoptive; Neoplasms; Treatment Outcome; Tumor Microenvironment
PubMed: 31754328
DOI: 10.7150/ijbs.34213 -
Blood Cancer Journal Feb 2021Progress in the understanding of the biology and therapy of acute myeloid leukemia (AML) is occurring rapidly. Since 2017, nine agents have been approved for various... (Review)
Review
Progress in the understanding of the biology and therapy of acute myeloid leukemia (AML) is occurring rapidly. Since 2017, nine agents have been approved for various indications in AML. These included several targeted therapies like venetoclax, FLT3 inhibitors, IDH inhibitors, and others. The management of AML is complicated, highlighting the need for expertise in order to deliver optimal therapy and achieve optimal outcomes. The multiple subentities in AML require very different therapies. In this review, we summarize the important pathophysiologies driving AML, review current therapies in standard practice, and address present and future research directions.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chromosome Aberrations; Disease Management; Humans; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Mutation; Prognosis; Protein Kinase Inhibitors
PubMed: 33619261
DOI: 10.1038/s41408-021-00425-3 -
Circulation Research May 2021Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and... (Review)
Review
Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.
Topics: Acute Disease; Body Fluids; Cardio-Renal Syndrome; Cardiotoxins; Comorbidity; Heart Failure; Hospitalization; Humans; Inflammation Mediators; Myocardial Contraction; Natriuretic Peptide, Brain; Patient Discharge; Patient Readmission; Renin-Angiotensin System; Symptom Assessment; Vascular Resistance; Vasoconstriction; Vasodilator Agents
PubMed: 33983837
DOI: 10.1161/CIRCRESAHA.121.318186 -
Nature Reviews. Immunology Mar 2020Cellular therapies using regulatory T (T) cells are currently undergoing clinical trials for the treatment of autoimmune diseases, transplant rejection and... (Review)
Review
Cellular therapies using regulatory T (T) cells are currently undergoing clinical trials for the treatment of autoimmune diseases, transplant rejection and graft-versus-host disease. In this Review, we discuss the biology of T cells and describe new efforts in T cell engineering to enhance specificity, stability, functional activity and delivery. Finally, we envision that the success of T cell therapy in autoimmunity and transplantation will encourage the clinical use of adoptive T cell therapy for non-immune diseases, such as neurological disorders and tissue repair.
Topics: Animals; Autoimmune Diseases; Cell- and Tissue-Based Therapy; Graft Rejection; Humans; Immunotherapy, Adoptive; T-Lymphocytes, Regulatory
PubMed: 31811270
DOI: 10.1038/s41577-019-0232-6 -
Frontiers in Endocrinology 2020Thyroid cancer is the most common endocrine cancer. The discovery of new biomarkers for thyroid cancer has significantly improved the understanding of the molecular... (Review)
Review
Thyroid cancer is the most common endocrine cancer. The discovery of new biomarkers for thyroid cancer has significantly improved the understanding of the molecular pathogenesis of thyroid cancer, thus allowing more personalized treatments for patients with thyroid cancer. Most of the recently discovered targeted therapies inhibit the known oncogenic mechanisms in thyroid cancer initiation and progression such as MAPK pathway, PI3K/Akt-mTOR pathways, or VEGF. Despite the significant advances in molecular testing and the discoveries of new and promising therapeutics, effective treatments for advanced and metastatic, iodine-refractory thyroid cancer are still lacking. Here, we aim to summarize the current understanding of the genetic alterations and the dysregulated pathways in thyroid cancer and to discuss the most recent targeted therapies and immunotherapy for advanced thyroid cancer with a promising anti-tumor activity and clinical benefit.
Topics: History, 21st Century; Humans; Immunotherapy; Molecular Targeted Therapy; Mutation; Signal Transduction; Therapies, Investigational; Thyroid Neoplasms
PubMed: 32528402
DOI: 10.3389/fendo.2020.00082 -
Biochimica Et Biophysica Acta Dec 2015Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of... (Review)
Review
Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLCs) and non-small cell lung carcinomas (NSCLCs). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation.
Topics: Animals; Drug Therapy; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Molecular Targeted Therapy; Neoplasm Proteins; Radiotherapy; Treatment Outcome
PubMed: 26297204
DOI: 10.1016/j.bbcan.2015.08.002 -
Molecular Therapy : the Journal of the... Feb 2021Hereditary diseases are caused by mutations in genes, and more than 7,000 rare diseases affect over 30 million Americans. For more than 30 years, hundreds of researchers... (Review)
Review
Hereditary diseases are caused by mutations in genes, and more than 7,000 rare diseases affect over 30 million Americans. For more than 30 years, hundreds of researchers have maintained that genetic modifications would provide effective treatments for many inherited human diseases, offering durable and possibly curative clinical benefit with a single treatment. This review is limited to gene therapy using adeno-associated virus (AAV) because the gene delivered by this vector does not integrate into the patient genome and has a low immunogenicity. There are now five treatments approved for commercialization and currently available, i.e., Luxturna, Zolgensma, the two chimeric antigen receptor T cell (CAR-T) therapies (Yescarta and Kymriah), and Strimvelis (the gammaretrovirus approved for adenosine deaminase-severe combined immunodeficiency [ADA-SCID] in Europe). Dozens of other treatments are under clinical trials. The review article presents a broad overview of the field of therapy by in vivo gene transfer. We review gene therapy for neuromuscular disorders (spinal muscular atrophy [SMA]; Duchenne muscular dystrophy [DMD]; X-linked myotubular myopathy [XLMTM]; and diseases of the central nervous system, including Alzheimer's disease, Parkinson's disease, Canavan disease, aromatic l-amino acid decarboxylase [AADC] deficiency, and giant axonal neuropathy), ocular disorders (Leber congenital amaurosis, age-related macular degeneration [AMD], choroideremia, achromatopsia, retinitis pigmentosa, and X-linked retinoschisis), the bleeding disorder hemophilia, and lysosomal storage disorders.
Topics: Animals; Clinical Studies as Topic; Combined Modality Therapy; Dependovirus; Gene Expression; Genetic Diseases, Inborn; Genetic Therapy; Genetic Vectors; Humans; Organ Specificity; Treatment Outcome
PubMed: 33309881
DOI: 10.1016/j.ymthe.2020.12.007 -
Nature Reviews. Clinical Oncology Aug 2022Structural imaging remains an essential component of diagnosis, staging and response assessment in patients with cancer; however, as clinicians increasingly seek to... (Review)
Review
Structural imaging remains an essential component of diagnosis, staging and response assessment in patients with cancer; however, as clinicians increasingly seek to noninvasively investigate tumour phenotypes and evaluate functional and molecular responses to therapy, theranostics - the combination of diagnostic imaging with targeted therapy - is becoming more widely implemented. The field of radiotheranostics, which is the focus of this Review, combines molecular imaging (primarily PET and SPECT) with targeted radionuclide therapy, which involves the use of small molecules, peptides and/or antibodies as carriers for therapeutic radionuclides, typically those emitting α-, β- or auger-radiation. The exponential, global expansion of radiotheranostics in oncology stems from its potential to target and eliminate tumour cells with minimal adverse effects, owing to a mechanism of action that differs distinctly from that of most other systemic therapies. Currently, an enormous opportunity exists to expand the number of patients who can benefit from this technology, to address the urgent needs of many thousands of patients across the world. In this Review, we describe the clinical experience with established radiotheranostics as well as novel areas of research and various barriers to progress.
Topics: Humans; Medical Oncology; Neoplasms; Precision Medicine; Radiopharmaceuticals
PubMed: 35725926
DOI: 10.1038/s41571-022-00652-y -
Cell Apr 2020Cell therapies present an entirely new paradigm in drug development. Within this class, immune cell therapies are among the most advanced, having already demonstrated... (Review)
Review
Cell therapies present an entirely new paradigm in drug development. Within this class, immune cell therapies are among the most advanced, having already demonstrated definitive evidence of clinical benefits in cancer and infectious disease. Numerous features distinguish these "living therapies" from traditional medicines, including their ability to expand and contract in proportion to need and to mediate therapeutic benefits for months or years following a single application. Continued advances in fundamental immunology, genetic engineering, gene editing, and synthetic biology exponentially expand opportunities to enhance the sophistication of immune cell therapies, increasing potency and safety and broadening their potential for treatment of disease. This perspective will summarize the current status of immune cell therapies for cancer, infectious disease, and autoimmunity, and discuss advances in cellular engineering to overcome barriers to progress.
Topics: Autoimmune Diseases; Cell Engineering; Cell- and Tissue-Based Therapy; Gene Editing; Genetic Engineering; Humans; Immunotherapy; Neoplasms; Synthetic Biology; Virus Diseases
PubMed: 32243795
DOI: 10.1016/j.cell.2020.03.001 -
Medicina (Kaunas, Lithuania) Jan 2022: Transcutaneous electrical stimulation of low- and medium-frequency currents is commonly used in pain management. Interferential current (IFC) therapy, a medium... (Review)
Review
: Transcutaneous electrical stimulation of low- and medium-frequency currents is commonly used in pain management. Interferential current (IFC) therapy, a medium frequency alternating current therapy that reportedly reduces skin impedance, can reach deeper tissues. IFC therapy can provide several different treatment possibilities by adjusting its parameters (carrier frequency, amplitudemodulated frequency, sweep frequency, sweep mode or swing pattern, type of application (bipolar or quadripolar), time of application and intensity). The objective of this review article is to discuss the literature findings on the analgesic efficacy of IFC therapy. : According to the literature, IFC therapy shows significant analgesic effects in patients with neck pain, low back pain, knee osteoarthritis and post-operative knee pain. Most of the IFC parameters seem not to influence its analgesic effects. We encourage further studies to investigate the mechanism of action of IFC therapy.
Topics: Analgesics; Electric Stimulation Therapy; Humans; Low Back Pain; Pain Management; Transcutaneous Electric Nerve Stimulation
PubMed: 35056448
DOI: 10.3390/medicina58010141