Development of CAR-NK Cells Targeting cSCC-Specific Antigens for Precision Immunotherapy.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer that is frequently diagnosed, is distinguished by its propensity for aggressive behavior, frequent poor response to standard therapy, and capacity to metastasize to distant areas. Utilizing the body's natural immune defense mechanisms, particularly through the use of chimeric antigen receptor (CAR) technology, is receiving increasing attention in the dynamic field of oncological therapies. Although T cells have received most of the attention, this strategy has proven to be highly effective in battling some blood-related malignancies. However, there are considerable challenges when using this method in the context of solid tumors. The innate immune system's natural killer (NK) cells are essential parts because they have the ability to detect and destroy cancer cells. CAR-NK cells are a very promising approach because they combine the natural cytotoxic properties of natural killer (NK) cells with the precise targeting skills of chimeric antigen receptor (CAR) technology. With the use of this integrated strategy, the intrinsic diversity of cutaneous squamous cell carcinoma (cSCC) tumors may be successfully targeted, increasing treatment effectiveness and lowering the risk of tumor recurrence. This tactic is improved by the development of dual-specificity chimeric antigen receptors (CARs), which fully resolve the antigen presentation heterogeneity among tumor cells. In conclusion, the use of CAR-NK cells that precisely target cSCC-specific antigens has the potential to drastically transform therapy approaches for cSCC as well as other difficult solid tumors as oncological research advances. In order to create chimeric antigen receptor (CAR)-natural killer (NK) cells that particularly target antigens linked to cutaneous squamous cell carcinoma (cSCC), the goal of this protocol is to present a detailed method. The ultimate objective is to lay the groundwork for the development of precision immunotherapy.

GMP-Based Isolation of Full-Term Human Placenta-Derived NK Cells for CAR-NK Cell Therapy in Malignant Melanoma.

Melanoma, a severe type of skin cancer, poses significant management challenges due to its resistance to available treatments. Despite this obstacle, the high immunogenicity of melanoma renders it amenable to immune therapy, and NK cells have been identified as possessing anti-tumor properties in immunotherapy. The development of chimeric antigen receptor (CAR)-modified NK cells, or CAR-NK cells, has shown potential in enhancing immunotherapeutic regimens. To achieve this, researchers have explored various sources of NK cells, including those derived from the placenta, which offers benefits compared to other sources due to their limited ex vivo expansion potential. Recent studies have indicated the capacity to expand functional NK cells from placenta-derived cells in vitro that possess anti-tumor cytolytic properties. This chapter discusses the isolation of full-term human placenta-derived NK cells using Good Manufacturing Practice-based methods for CAR-NK cell therapy in melanoma.

Application of Biocompatible Scaffolds in Stem-Cell-Based Dental Tissue Engineering.

Tissue engineering as an important field in regenerative medicine is a promising therapeutic approach to replace or regenerate injured tissues. It consists of three vital steps including the selection of suitable cells, formation of 3d scaffolds, and adding growth factors. Mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs) are mentioned as two main sources for this approach that have been used for the treatment of various types of disorders. However, the main focus of literature in the field of dental tissue engineering is on utilizing MSCs. On the other hand, biocompatible scaffolds play a notable role in this regenerative process which is mentioned to be harmless with acceptable osteoinductivity. Their ability in inhibiting inflammatory responses also makes them powerful tools. Indeed, stem cell functions should be supported by biomaterials acting as scaffolds incorporated with biological signals. Naturally derived polymeric scaffolds and synthetically engineered polymeric/ceramic scaffolds are two main types of scaffolds regarding their materials that are defined further in this review. Various strategies of tissue bioengineering can affect the regeneration of dentin-pulp complex, periodontium regeneration, and whole teeth bioengineering. In this regard, in vivo/ex vivo experimental models have been developed recently in order to perform preclinical studies of dental tissue engineering which make it more transferable to be used for clinic uses. This review summarizes dental tissue engineering through its different components. Also, strategies of tissue bioengineering and experimental models are introduced in order to provide a perspective of the potential roles of dental tissue engineering to be used for clinical aims.

Regenerative Medicine for the Treatment of Ischemic Heart Disease; Status and Future Perspectives.

Cardiovascular disease is now the leading cause of adult death in the world. According to new estimates from the World Health Organization, myocardial infarction (MI) is responsible for four out of every five deaths due to cardiovascular disease. Conventional treatments of MI are taking aspirin and nitroglycerin as intermediate treatments and injecting antithrombotic agents within the first 3 h after MI. Coronary artery bypass grafting and percutaneous coronary intervention are the most common long term treatments. Since none of these interventions will fully regenerate the infarcted myocardium, there is value in pursuing more innovative therapeutic approaches. Regenerative medicine is an innovative interdisciplinary method for rebuilding, replacing, or repairing the missed part of different organs in the body, as similar as possible to the primary structure. In recent years, regenerative medicine has been widely utilized as a treatment for ischemic heart disease (one of the most fatal factors around the world) to repair the lost part of the heart by using stem cells. Here, the development of mesenchymal stem cells causes a breakthrough in the treatment of different cardiovascular diseases. They are easily obtainable from different sources, and expanded and enriched easily, with no need for immunosuppressing agents before transplantation, and fewer possibilities of genetic abnormality accompany them through multiple passages. The production of new cardiomyocytes can result from the transplantation of different types of stem cells. Accordingly, due to its remarkable benefits, stem cell therapy has received attention in recent years as it provides a drug-free and surgical treatment for patients and encourages a more safe and feasible cardiac repair. Although different clinical trials have reported on the promising benefits of stem cell therapy, there is still uncertainty about its mechanism of action. It is important to conduct different preclinical and clinical studies to explore the exact mechanism of action of the cells. After reviewing the pathophysiology of MI, this study addresses the role of tissue regeneration using various materials, including different types of stem cells. It proves some appropriate data about the importance of ethical problems, which leads to future perspectives on this scientific method.

The Outcome of Stem Cell-Based Therapies on the Immune Responses in Rheumatoid Arthritis.

Rheumatoid arthritis as a common autoimmune inflammatory disorder with unknown etiology can affect 0.5-1% of adults in developed countries. It involves more than just the patient's joints and can be accompanied by several comorbidities and affect cardiovascular, pulmonary, and some other systems of the human body. Although cytokine-mediated pathways are mentioned to have a central role in RA pathogenesis, adaptive and innate immune systems and intracellular signaling pathways all have important roles in this process. Non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying anti-rheumatic drugs, and biological agents are some mentioned medications used for RA. They are accompanied by some adverse effects and treatment failures which elucidates the needing for novel and more powerful therapeutic approaches. Stem cell-based therapies and their beneficial effects on therapeutic processes of different diseases have been founded so far. They can be an alternative and promising therapeutic approach for RA, too; due to their effects on immune responses of the disease. This review, besides some explanations about RA characteristics, addresses the outcome of the stem cell-based therapies including mesenchymal stem cell transplantation and hematopoietic stem cell transplantation for RA and explains their effects on the disease improvement.