Breaking the shield of solid tumors: a combined approach for enhanced efficacy of CAR-T cells.

The use of chimeric antigen receptor (CAR)-T cells has enhanced the range of available therapeutic modalities in the context of cancer treatment. CAR-T cells have demonstrated considerable efficacy in the targeted eradication of blood cancer cells, thereby stimulating substantial interest in the advancement of such therapeutic approaches. However, the efficacy of CAR-T cells against solid tumor cells has been limited due to the presence of various obstacles.

Cell-Based Therapy and Genome Editing as Emerging Therapeutic Approaches to Treat Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints. Although much remains unknown about the pathogenesis of RA, there is evidence that impaired immune tolerance and the development of RA are related. And it is precisely the restoration of immune tolerance at the site of the inflammation that is the ultimate goal of the treatment of RA.

Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation.

Systemic lupus erythematosus (SLE) is characterized by a systemic dysfunction of the innate and adaptive immune systems, leading to an attack on healthy tissues of the body. During the development of SLE, pathogenic features, such as the formation of autoantibodies to self-nuclear antigens, caused tissue damage including necrosis and fibrosis, with an increased expression of type Ⅰ interferon (IFN) regulated genes. Treatment of lupus with immunosuppressants and glucocorticoids, which are used as the standard therapy, is not effective enough and causes side effects.

Immunotherapy Strategy for Systemic Autoimmune Diseases: Betting on CAR-T Cells and Antibodies.

Systemic autoimmune diseases (SAIDs), such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA), are fully related to the unregulated innate and adaptive immune systems involved in their pathogenesis. They have similar pathogenic characteristics, including the interferon signature, loss of tolerance to self-nuclear antigens, and enhanced tissue damage like necrosis and fibrosis. Glucocorticoids and immunosuppressants, which have limited specificity and are prone to tolerance, are used as the first-line therapy.

Recent Advances in the Development of Bioreactors for Manufacturing of Adoptive Cell Immunotherapies.

Harnessing the human immune system as a foundation for therapeutic technologies capable of recognizing and killing tumor cells has been the central objective of anti-cancer immunotherapy. In recent years, there has been an increasing interest in improving the effectiveness and accessibility of this technology to make it widely applicable for adoptive cell therapies (ACTs) such as chimeric antigen receptor T (CAR-T) cells, tumor infiltrating lymphocytes (TILs), dendritic cells (DCs), natural killer (NK) cells, and many other. Automated, scalable, cost-effective, and GMP-compliant bioreactors for production of ACTs are urgently needed.

Knowns and Unknowns about CAR-T Cell Dysfunction.

Immunotherapy using chimeric antigen receptor (CAR) T cells is a promising option for cancer treatment. However, T cells and CAR-T cells frequently become dysfunctional in cancer, where numerous evasion mechanisms impair antitumor immunity. Cancer frequently exploits intrinsic T cell dysfunction mechanisms that evolved for the purpose of defending against autoimmunity.

Adoptive Immunotherapy beyond CAR T-Cells.

Adoptive cell immunotherapy (ACT) is a vibrant field of cancer treatment that began progressive development in the 1980s. One of the most prominent and promising examples is chimeric antigen receptor (CAR) T-cell immunotherapy for the treatment of B-cell hematologic malignancies. Despite success in the treatment of B-cell lymphomas and leukemia, CAR T-cell therapy remains mostly ineffective for solid tumors.

Application of CAR-T Cell Therapy beyond Oncology: Autoimmune Diseases and Viral Infections.

Adoptive cell transfer (ACT) has long been at the forefront of the battle with cancer that began last century with the therapeutic application of tumor-infiltrating lymphocytes (TILs) against melanoma. The development of novel ACT approaches led researchers and clinicians to highly efficient technologies based on genetically engineered T lymphocytes, with chimeric antigen receptor (CAR)-T cells as the most prominent example. CARs consist of an extracellular domain that represents the single-chain variable fragment (scFv) of a monoclonal antibody (mAb) responsible for target recognition and the intracellular domain, which was built from up to several signaling motifs that mediated T cell activation.

Key Players in the Mutant p53 Team: Small Molecules, Gene Editing, Immunotherapy.

The transcription factor p53 is a key tumor suppressor that is inactivated in almost all cancers due to either point mutations in the gene or overexpression of its negative regulators. The p53 protein is known as the "cellular gatekeeper" for its roles in facilitating DNA repair, cell cycle arrest or apoptosis upon DNA damage. Most p53 mutations are missense and result in either structural destabilization of the protein, causing its partial unfolding and deactivation under physiological conditions, or impairment of its DNA-binding properties.

Advancing CAR T-Cell Therapy for Solid Tumors: Lessons Learned from Lymphoma Treatment.

Chimeric antigen receptor (CAR) immunotherapy is one of the most promising modern approaches for the treatment of cancer. To date only two CAR T-cell products, Kymriah and Yescarta, have been approved by the Food and Drug Administration (FDA) for the treatment of lymphoblastic leukemia and B-cell lymphoma. Administration of CAR T-cells to control solid tumors has long been envisaged as one of the most difficult therapeutic tasks.

Promising new therapeutic targets for regulation of inflammation and immunity: RING-type E3 ubiquitin ligases.

Ubiquitin-proteasome system (UPS) is a primary signaling pathway for regulation of protein turnover and removal of misfolded proteins in eukaryotic cells. Enzymes of the UPS pathway - E1 activating, E2 conjugating, E3 ligating - act together to covalently tag substrate proteins with a chain of ubiquitins, small regulatory proteins. The poly-ubiquitin chain then serves as a recognition motif for 26S proteasome to recognize and degrade the substrate.

Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as Targets.

Ubiquitin-proteasome system (UPS) is a primary signaling pathway for regulation of intracellular protein levels. E3 ubiquitin ligases, substrate-specific members of the UPS, represent highly attractive protein targets for drug discovery. The importance of E3 ligases as prospective targets for small molecule modulation is reinforced by ever growing evidence of their role in cancer and other diseases.

High Triglycerides Are Associated with Low Thrombocyte Counts and High VEGF in Nephropathia Epidemica.

Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome. Several reports have demonstrated a severe alteration in lipoprotein metabolism. However, little is known about changes in circulating lipids in NE.