For nearly three decades, chimeric antigen receptors (CARs) have captivated the interest of researchers seeking to find novel immunotherapies to treat cancer. CARs were first designed to work with T cells, and the first CAR T cell therapy was approved to treat B cell lymphoma in 2017. Recent advancements in CAR technology have led to the development of modified CARs, including multi-specific CARs and logic gated CARs. Other immune cell types, including natural killer (NK) cells and macrophages, have also been engineered to express CARs to treat cancer. Additionally, CAR technology has been adapted in novel approaches to treating autoimmune disease and other conditions and diseases. In this article, we review these recent advancements in alternative CAR therapies and design, as well as their mechanisms of action, challenges in application, and potential future directions.
Chimeric antigen receptor (CAR) T cells are an exciting advancement in cancer immunotherapy, with striking success in hematological cancers. However, in solid tumors, the unique immunosuppressive elements of the tumor microenvironment (TME) contribute to the failure of CAR T cells. This review discusses the cell populations, cytokine/chemokine profile, and metabolic immunosuppressive elements of the TME. This immunosuppressive TME causes CAR T-cell exhaustion and influences failure of CAR T cells to successfully infiltrate solid tumors. Recent advances in CAR T-cell development, which seek to overcome aspects of the TME immunosuppression, are also reviewed. Novel discoveries overcoming immunosuppressive limitations of the TME may lead to the success of CAR T cells in solid tumors.
The genetic and molecular basis of flagellar motility has been investigated for several decades, with innovative research strategies propelling advances at a steady pace. Furthermore, as the phenomenon is examined in diverse bacteria, new taxon-specific regulatory and structural features are being elucidated. Motility is also a straightforward bacterial phenotype that can allow undergraduate researchers to explore the palette of molecular genetic tools available to microbiologists. This study, driven primarily by undergraduate researchers, evaluated hundreds of flagellar motility mutants in the Gram-negative plant-associated bacterium Agrobacterium fabrum. The nearly saturating screen implicates a total of 37 genes in flagellar biosynthesis, including genes of previously unknown function.
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