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Multipurposing CARs: Same engine, different vehicles.

ABSTRACT: T cells genetically engineered to recognize and eliminate tumor cells through synthetic chimeric antigen receptors (CARs) have demonstrated remarkable clinical efficacy against B cell leukemia over the past decade. This therapy is a form of highly personalized medicine that involves genetically modifying a patient's T cells to recognize and kill cancer cells. With the FDA approval of 5 CAR T cell products, this approach has been validated as a powerful new drug in the therapeutic armamentarium against cancer. Researchers are now studying how to expand this technology beyond its use in conventional polyclonal αβ T cells to address limitations to the current therapy in cancer and applications beyond it. Considering the specific characteristics of immune cell from diverse lineages, several preclinical and clinical studies are under way to assess the advantages of CAR-redirected function in these cells and apply the lessons learned from CAR T cell therapy in cancer to other diseases.

SUBMITTER: Hossian AKMN

PROVIDER: S-EPMC9077369 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Multipurposing CARs: Same engine, different vehicles.

Hossian A K M Nawshad AKMN Hackett Christopher S CS Brentjens Renier J RJ Rafiq Sarwish S

Molecular therapy : the journal of the American Society of Gene Therapy 20220211 4

T cells genetically engineered to recognize and eliminate tumor cells through synthetic chimeric antigen receptors (CARs) have demonstrated remarkable clinical efficacy against B cell leukemia over the past decade. This therapy is a form of highly personalized medicine that involves genetically modifying a patient's T cells to recognize and kill cancer cells. With the FDA approval of 5 CAR T cell products, this approach has been validated as a powerful new drug in the therapeutic armamentarium a ...[more]

PMID: 35151842

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Project description:We explore the relationship between first language attrition and language dominance, defined here as the relative availability of each of a bilingual's languages with respect to language processing. We assume that both processes might represent two stages of one and the same phenomenon (Schmid and Köpke, 2017; Köpke, 2018). While many researchers agree that language dominance changes repeatedly over the lifespan (e.g., Silva-Corvalan and Treffers-Daller, 2015), little is known about the precise time scales involved in dominance shifts and attrition. We investigate these time scales in a longitudinal case study of pronominal subject production by a near-native L2-German (semi-null subject and topic-drop but non-pro-drop) and L1-Bulgarian (pro-drop) bilingual speaker with 17 years of residence in Germany. This speaker's spontaneous speech showed a significantly higher rate of overt pronominal subjects in her L1 than the controls' rates when tested in Germany. After 3 weeks of L1-reexposure in Bulgaria, however, attrition effects disappeared and the overt subject rate fell within the monolinguals' range (Genevska-Hanke, 2017). The findings of this first investigation are now compared to those of a second investigation 5 years later, involving data collection in both countries with the result that after 17 years of immigration, no further attrition was attested and the production of overt subjects remained monolingual-like for the data collections in both language environments. The discussion focuses on the factors that are likely to explain these results. First, these show that attrition and language dominance are highly dependent on immediate language use context and change rapidly when the language environment is modified. Additionally, the data obtained after L1-reexposure illustrate that time scales involved in dominance shift or attrition are much shorter than previously thought. Second, the role of age of acquisition in attrition has repeatedly been acknowledged. The present study demonstrates that attrition of a highly entrenched L1 is a phenomenon affecting language processing only temporarily and that it is likely to regress quickly after reexposure or return to balanced L1-use. The discussion suggests that dominance shift and attrition probably involve similar mechanisms and are influenced by the same external factors, showing that both may be different steps of the same process.

Project description:Symbioses in marine sponges involve diverse consortia of microorganisms that contribute to the health and ecology of their hosts. The microbial communities of 13 taxonomically diverse Great Barrier Reef (GBR) sponge species were assessed by DGGE and 16S rRNA gene sequencing to determine intra and inter species variation in bacterial symbiont composition. Microbial profiling revealed communities that were largely conserved within different individuals of each species with intra species similarity ranging from 65-100%. 16S rRNA gene sequencing revealed that the communities were dominated by Proteobacteria, Chloroflexi, Acidobacteria, Actinobacteria, Nitrospira, and Cyanobacteria. Sponge-associated microbes were also highly host-specific with no operational taxonomic units (OTUs) common to all species and the most ubiquitous OTU found in only 5 of the 13 sponge species. In total, 91% of the OTUs were restricted to a single sponge species. However, GBR sponge microbes were more closely related to other sponge-derived bacteria than they were to environmental communities with sequences falling within 50 of the 173 previously defined sponge-(or sponge-coral) specific sequence clusters (SC). These SC spanned the Acidobacteria, Actinobacteria, Proteobacteria, Bacteroidetes, Chloroflexi, Cyanobacteria, Gemmatimonadetes, Nitrospira, and the Planctomycetes-Verrucomicrobia-Chlamydiae superphylum. The number of sequences assigned to these sponge-specific clusters across all species ranged from 0 to 92%. No relationship between host phylogeny and symbiont communities were observed across the different sponge orders, although the highest level of similarity was detected in two closely related Xestospongia species. This study identifies the core microbial inhabitants in a range of GBR sponges thereby providing the basis for future studies on sponge symbiotic function and research aiming to predict how sponge holobionts will respond to environmental perturbation.

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Multipurposing CARs: Same engine, different vehicles.

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Multipurposing CARs: Same engine, different vehicles.

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