CAR T cell therapy as a promising approach in cancer immunotherapy: challenges and opportunities.

BACKGROUND: Chimeric antigen receptor (CAR)-modified T cell therapy has shown great potential in the immunotherapy of patients with hematologic malignancies. In spite of this striking achievement, there are still major challenges to overcome in CAR T cell therapy of solid tumors, including treatment-related toxicity and specificity. Also, other obstacles may be encountered in tackling solid tumors, such as their immunosuppressive microenvironment, the heterogeneous expression of cell surface markers, and the cumbersome arrival of T cells at the tumor site. Although several strategies have been developed to overcome these challenges, aditional research aimed at enhancing its efficacy with minimum side effects, the design of precise yet simplified work flows and the possibility to scale-up production with reduced costs and related risks is still warranted. CONCLUSIONS: Here, we review main strategies to establish a balance between the toxicity and activity of CAR T cells in order to enhance their specificity and surpass immunosuppression. In recent years, many clinical studies have been conducted that eventually led to approved products. To date, the FDA has approved two anti-CD19 CAR T cell products for non-Hodgkin lymphoma therapy, i.e., axicbtagene ciloleucel and tisagenlecleucel. With all the advances that have been made in the field of CAR T cell therapy for hematologic malignancies therapy, ongoing studies are focused on optimizing its efficacy and specificity, as well as reducing the side effects. Also, the efforts are poised to broaden CAR T cell therapeutics for other cancers, especially solid tumors.

Stem Cell-Derived Exosomes: a New Strategy of Neurodegenerative Disease Treatment.

Short-term symptomatic treatment and dose-dependent side effects of pharmacological treatment for neurodegenerative diseases have forced the medical community to seek an effective treatment for this serious global health threat. Therapeutic potential of stem cell for treatment of neurodegenerative disorders was identified in 1980 when fetal nerve tissue was used to treat Parkinson's disease (PD). Then, extensive studies have been conducted to develop this treatment strategy for neurological disease therapy. Today, stem cells and their secretion are well-known as a therapeutic environment for the treatment of neurodegenerative diseases. This new paradigm has demonstrated special characteristics related to this treatment, including neuroprotective and neurodegeneration, remyelination, reduction of neural inflammation, and recovery of function after induced injury. However, the exact mechanism of stem cells in repairing nerve damage is not yet clear; exosomes derived from them, an important part of their secretion, are introduced as responsible for an important part of such effects. Numerous studies over the past few decades have evaluated the therapeutic potential of exosomes in the treatment of various neurological diseases. In this review, after recalling the features and therapeutic history, we will discuss the latest stem cell-derived exosome-based therapies for these diseases.

miRNA as promising theragnostic biomarkers for predicting radioresistance in cancer: A systematic review and meta-analysis.

Radioresistance remains as an obstacle in cancer treatment. This systematic review and meta-analysis aimed to evaluate the association between the expression of miRNAs and responses to radiotherapy and the prognosis of different tumors. In total, 77 miRNAs in 19 cancer types were studied, in which 24 miRNAs were upregulated and 58 miRNAs were downregulated in cancer patients. Five miRNAs were differentially expressed. Moreover, 75 miRNAs were found to be related to radioresistance, while 5 were observed to be related to radiosensitivity. The pooled HR and 95 % confidence interval for the combined studies was 1.135 (0.819-1.574; P-value = 0.4). The HR values of the subgroup analysis for miR-21 (HR = 2.344; 95 % CI: 1.927-2.850; P-value = 0.000), nasopharyngeal carcinoma (HR = 0.448; 95 % CI: 0.265-0.760; P = 0.003) and breast cancer (HR = 1.131; 95 % CI: 0.311-4.109; P = .85) were obtained. Our results highlighted that across the published literature, miRNAs can modulate tumor radioresistance or sensitivity by affecting radiation-related signaling pathways. It seems that miRNAs could be considered as a theragnostic biomarker to predict and monitor clinical response to radiotherapy. Thus, the prediction of radioresistance in malignant patients will improve radiotherapy outcomes and radiotherapeutic resistance.

The Use of Mesenchymal Stem Cells and their Derived Extracellular Vesicles in Cardiovascular Disease Treatment.

BACKGROUND: Cardiovascular disease (CVD), including disorders of cardiac muscle and vascular, is the major cause of death globally. Many unsuccessful attempts have been made to intervene in the disease's pathogenesis and treatment. Stem cell-based therapies, as a regeneration strategy, cast a new hope for CVD treatment. One of the most well-known stem cells is mesenchymal stem cells (MSCs), classified as one of the adult stem cells and can be obtained from different tissues. These cells have superior properties, such as proliferation and highly specialized differentiation. On the other hand, they have the potential to modulate the immune system and anti-inflammatory activity. One of their most important features is the secreting the extracellular vesicles (EVs) like exosomes (EXOs) as an intercellular communication system mediating the different physiological and pathophysiological affairs. METHODS: In this review study, the importance of MSC and its secretory exosomes for the treatment of heart disease has been together and specifically addressed and the use of these promising natural and accessible agents is predicted to replace the current treatment modalities even faster than we imagine. RESULTS: MSC derived EXOs by providing a pro-regenerative condition allowing innate stem cells to repair damaged tissues successfully. As a result, MSCs are considered as the appropriate cellular source in regenerative medicine. In the plethora of experiments, MSCs and MSC-EXOs have been used for the treatment and regeneration of heart diseases and myocardial lesions. CONCLUSION: Administration of MSCs has been provided a replacement therapeutic option for heart regeneration, obtaining great attention among the basic researcher and the medical doctors.

Stem Cell Aging in Lifespan and Disease: A State-of-the-Art Review.

Aging is considered as inevitable changes at different levels of genome, cell, and organism. From the accumulation of DNA damages to imperfect protein homeostasis, altered cellular communication and exhaustion of stem cells, aging is a major risk factor for many prevalent diseases, such as cancer, cardiovascular disease, pulmonary disease, diabetes, and neurological disorders. The cells are dynamic systems, which, through a cycle of processes such as replication, growth, and death, could replenish the bodies' organs and tissues, keeping an entire organism in optimal working order. In many different tissues, adult stem cells are behind these processes, replenishing dying cells to maintain normal tissue function and regenerating injured tissues. Therefore, adult stem cells play a vital role in preventing the aging of organs and tissues, and can delay aging. However, during aging, these cells also undergo some detrimental changes such as alterations in the microenvironment, a decline in the regenerative capacity, and loss of function. This review aimed to discuss age-related changes of stem cells in different tissues and cells, including skin, muscles, brain, heart, hair follicles, liver, and lung.