Development of Stable CHO-K1 Cell Lines Overexpressing Full-Length Human CD20 Antigen.

Background: CD20 is a differentiation-related antigen exclusively expressed on the membrane of B lymphocytes. CD20 amplification is observed in numerous immune-related disorders, making it an ideal target for immunotherapy of hematological malignancies and autoimmune diseases. MAb-based therapies targeting CD20 have a principal role in the treatment of several immune-related disordes and cancers, including CLL. Fc gamma receptors mediate CD20 internalization in hematopoietic cells; therefore, this study aimed to establish non-hematopoietic stable cell lines overexpressing full-length human CD20 antigen as an in vitro model for CD20-related studies. Methods: CD20 gene was cloned into the transfer vector. The lentivirus system was transfected to packaging HEK 293T cells, and the supernatants were harvested. CHO-K1 cells were transduced using recombinant viruses, and a stable cell pool was developed by the antibiotic selection. CD20 expression was confirmed at the mRNA and protein levels. Results: Simultaneous expression of GFP protein facilitated the detection of CD20-expressing cells. Immunophenotyping analysis of stable clones demonstrated expression of CD20 antigen. In addition, the mean fluorescence intensity was significantly higher in the CD20-CHO-K1 clones than the wild-type CHO-K1 cells. Conclusion: This study is the first report on using second-generation lentiviral vectors for the establishment of a non-hematopoietic cell-based system, which stably expresses full-length human CD20 antigen. Results of stable CHO cell lines with different levels of CD20 antigen are well suited to be used for CD20-based investigations, including binding and functional assays.

Update on immune-based therapy strategies targeting cancer stem cells.

Accumulating data reveals that tumors possess a specialized subset of cancer cells named cancer stem cells (CSCs), responsible for metastasis and recurrence of malignancies, with various properties such as self-renewal, heterogenicity, and capacity for drug resistance. Some signaling pathways or processes like Notch, epithelial to mesenchymal transition (EMT), Hedgehog (Hh), and Wnt, as well as CSCs' surface markers such as CD44, CD123, CD133, and epithelial cell adhesion molecule (EpCAM) have pivotal roles in acquiring CSCs properties. Therefore, targeting CSC-related signaling pathways and surface markers might effectively eradicate tumors and pave the way for cancer survival. Since current treatments such as chemotherapy and radiation therapy cannot eradicate all of the CSCs and tumor relapse may happen following temporary recovery, improving novel and more efficient therapeutic options to combine with current treatments is required. Immunotherapy strategies are the new therapeutic modalities with promising results in targeting CSCs. Here, we review the targeting of CSCs by immunotherapy strategies such as dendritic cell (DC) vaccines, chimeric antigen receptors (CAR)-engineered immune cells, natural killer-cell (NK-cell) therapy, monoclonal antibodies (mAbs), checkpoint inhibitors, and the use of oncolytic viruses (OVs) in pre-clinical and clinical studies. This review will mainly focus on blood malignancies but also describe solid cancers.

Immune checkpoint inhibitors promising role in cancer therapy: clinical evidence and immune-related adverse events.

The advent of immune checkpoint inhibitors (ICIs) has led to noteworthy progressions in the management of diverse cancer types, as evidenced by the pioneering "ipilimumab" medication authorized by US FDA in 2011. Importantly, ICIs agents have demonstrated encouraging potential in bringing about transformation across diverse forms of cancer by selectively targeting the immune checkpoint pathways that are exploited by cancerous cells for dodging the immune system, culminating in progressive and favorable health outcomes for patients. The primary mechanism of action (MOA) of ICIs involves blocking inhibitory immune checkpoints. There are three approved categories including Programmed Death (PD-1) inhibitors (cemiplimab, nivolumab, and pembrolizumab), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (Ipilimumab), and Programmed Death-Ligand 1 (PDL-1) (Avelumab). Although ICIs promisingly increase therapeutic response and cancer survival rates, using ICIs has demonstrated some limitations including autoimmune reactions and toxicities, requiring close monitoring. The present review endeavors to explicate the underlying principles of the MOA and pharmacokinetics of the approved ICIs in the realm of cancer induction, including an appraisal of their level of practice-based evidence.

Long Non-Coding RNAs as Novel Targets for Phytochemicals to Cease Cancer Metastasis.

Metastasis is a multi-step phenomenon during cancer development leading to the propagation of cancer cells to distant organ(s). According to estimations, metastasis results in over 90% of cancer-associated death around the globe. Long non-coding RNAs (LncRNAs) are a group of regulatory RNA molecules more than 200 base pairs in length. The main regulatory activity of these molecules is the modulation of gene expression. They have been reported to affect different stages of cancer development including proliferation, apoptosis, migration, invasion, and metastasis. An increasing number of medical data reports indicate the probable function of LncRNAs in the metastatic spread of different cancers. Phytochemical compounds, as the bioactive agents of plants, show several health benefits with a variety of biological activities. Several phytochemicals have been demonstrated to target LncRNAs to defeat cancer. This review article briefly describes the metastasis steps, summarizes data on some well-established LncRNAs with a role in metastasis, and identifies the phytochemicals with an ability to suppress cancer metastasis by targeting LncRNAs.

Naringenin: A potential flavonoid phytochemical for cancer therapy.

Naringenin is an important phytochemical which belongs to the flavanone group of polyphenols, and is found mainly in citrus fruits like grapefruits and others such as tomatoes and cherries plus medicinal plants derived food. Available evidence demonstrates that naringenin, as herbal medicine, has important pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. Collected data from in vitro and in vivo studies show the inactivation of carcinogens after treatment with pure naringenin, naringenin-loaded nanoparticles, and also naringenin in combination with anti-cancer agents in various malignancies, such as colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancer, bladder neoplasms, gastric cancer, and osteosarcoma. Naringenin inhibits cancer progression through multiple mechanisms, like apoptosis induction, cell cycle arrest, angiogenesis hindrance, and modification of various signaling pathways including Wnt/ß-catenin, PI3K/Akt, NF-ĸB, and TGF-ß pathways. In this review, we demonstrate that naringenin is a natural product with potential for the treatment of different types of cancer, whether it is used alone, in combination with other agents, or in the form of the naringenin-loaded nanocarrier, after proper technological encapsulation.

Exosome application in tumorigenesis: diagnosis and treatment of melanoma.

Melanoma is the most aggressive of skin cancer derived from genetic mutations in the melanocytes. Current therapeutic approaches include surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy, and targeted therapy. However, the efficiency of these strategies may be decreased due to the development of diverse resistance mechanisms. Here, it has been proven that therapeutic monoclonal antibodies (mAbs) can improve the efficiency of melanoma therapies and also, cancer vaccines are another approach for the treatment of melanoma that has already improved clinical outcomes in these patients. The use of antibodies and gene vaccines provides a new perspective in melanoma treatment. Since the tumor microenvironment is another important factor for cancer progression and metastasis, in recent times, a mechanism has been identified to provide an opportunity for melanoma cells to communicate with remote cells. This mechanism is involved by a novel molecular structure, named extracellular vesicles (EVs). Depending on the functional status of origin cells, exosomes contain various cargos and different compositions. In this review, we presented recent progress of exosome applications in the treatment of melanoma. Different aspects of exosome therapy and ongoing efforts in this field will be discussed too.

Recent Advances in Understanding the Pathogenesis of Rheumatoid Arthritis: New Treatment Strategies.

Rheumatoid arthritis (RA) is considered a chronic systemic, multi-factorial, inflammatory, and progressive autoimmune disease affecting many people worldwide. While patients show very individual courses of disease, with RA focusing on the musculoskeletal system, joints are often severely affected, leading to local inflammation, cartilage destruction, and bone erosion. To prevent joint damage and physical disability as one of many symptoms of RA, early diagnosis is critical. Auto-antibodies play a pivotal clinical role in patients with systemic RA. As biomarkers, they could help to make a more efficient diagnosis, prognosis, and treatment decision. Besides auto-antibodies, several other factors are involved in the progression of RA, such as epigenetic alterations, post-translational modifications, glycosylation, autophagy, and T-cells. Understanding the interplay between these factors would contribute to a deeper insight into the causes, mechanisms, progression, and treatment of the disease. In this review, the latest RA research findings are discussed to better understand the pathogenesis, and finally, treatment strategies for RA therapy are presented, including both conventional approaches and new methods that have been developed in recent years or are currently under investigation.

TCR-like CARs and TCR-CARs targeting neoepitopes: an emerging potential.

Neoepitopes or neoantigens are a spectrum of unique mutations presented in a particular patient's tumor. Neoepitope-based adoptive therapies have the potential of tumor eradication without undue damaging effect on normal tissues. In this context, methods based on the T cell receptor (TCR) engineering or chimeric antigen receptors (CARs) have shown great promise. This review focuses on the TCR-like CARs and TCR-CARs directed against tumor-derived epitopes, with a concerted view on neoepitopes. We also address the current limitations of the field to know how to harness the full benefits of this approach and thereby design a sustained and specific antitumor therapy.

The immunology of SARS-CoV-2 infection, the potential antibody based treatments and vaccination strategies.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a potentially fatal agent for a new emerging viral disease (COVID-19) is of great global public health emergency. Herein, we represented potential antibody-based treatments especially monoclonal antibodies (mAbs) that may exert a potential role in treatment as well as developing vaccination strategies against COVID-19.Areas covered: We used PubMed, Google Scholar, and clinicaltrials.gov search strategies for relevant papers. We demonstrated some agents with potentially favorable efficacy as well as favorable safety. Several therapies are under assessment to evaluate their efficacy and safety for COVID19. However, the development of different strategies such as SARS-CoV-2-based vaccines and antibody therapy are urgently required beside other effective therapies such as plasma, anticoagulants, and immune as well as antiviral therapies. We encourage giving more attention to antibody-based treatments as an immediate strategy. Although there has not been any approved specific vaccine until now, developing vaccination strategies may have a protective effect against COVID-19.Expert opinion: An antiviral mAbs could be a safe and high-quality therapeutic intervention which is greatly recommended for COVID-19. Additionally, the high sequence homology between the SARS-CoV-2 and SARS/MERS viruses could shed light on developing to design a vaccine against SARS-CoV-2.

Statins: Complex outcomes but increasingly helpful treatment options for patients.

Statins are long known class of medicines and the most frequently prescribed drugs in cardiovascular pharmacotherapy, widely ordered not only in patients suffering from dyslipidemia, but also in patients with coronary artery disease, acute coronary syndromes, diabetes mellitus, stroke, hypertension, and chronic kidney disease, with or without coexisting dyslipidemia. However, several clinical trials have shown, that the advantages of statins goes beyond their reduction of the cholesterol level. Some crucial isoprenoid mediators which are highly essential for the activation of different intracellular/signaling proteins, that play important roles in multiple cellular mechanisms, are regulated by statins in addition to the inhibition of cholesterol biosynthesis. Moreover, anti-inflammatory intermediates and cytokines such as c-reactive protein, IL1, IL6, IL8, TNFA are affected downstream targets. Still, these numerous effects of statins such as anti-inflammatory effects, antioxidant effects, anti-proliferative, apoptotic, cell cycle regulatory and immunomodulatory effects, are primarily seen in conjunction with the inhibition of the HMG-CoA reductase. Other direct targets are missing. Beyond the classical application of statins, they were also tested to treat cancer with promising prospects, but still on a level of an adjuvant therapy option. Nevertheless the growing number of cancer studies and the increasing number of molecular players in affected pathways illustrates, that statins might be helpful in cancer therapeutics, despite the major part of the biological reaction network, which is regulated by statins, remains sketchy. It seems, that the statins still have some potential to improve established therapeutic procedures.