Background: Chimeric antigen receptor (CAR)-T cell therapies targeting glioblastoma (GBM)-associated antigens such as interleukin-13 receptor subunit alpha-2 (IL-13Rα2) have achieved limited clinical efficacy to date, in part due to an immunosuppressive tumor microenvironment (TME) characterized by inhibitory molecules such as transforming growth factor-beta (TGF-β). The aim of this study was to engineer more potent GBM-targeting CAR-T cells by countering TGF-β-mediated immune suppression in the TME.
Methods: We engineered a single-chain, bispecific CAR targeting IL-13Rα2 and TGF-β, which programs tumor-specific T cells to convert TGF-β from an immunosuppressant to an immunostimulant.
Patients with giant adenomas are more likely to have tumor extension into the paranasal sinuses. Compared to macroadenomas, giant adenomas are not associated with worse preoperative SNOT-22 scores.
View Article and Find Full Text PDFBackground: Migratory disc herniations can mimic neoplasms clinically and on imaging. Far lateral lumbar disc herniations usually compress the exiting nerve root and can be challenging to distinguish from a nerve sheath tumor due to the proximity of the nerve and characteristics on magnetic resonance imaging (MRI). These lesions can occasionally present in the upper lumbar spine region at the L1-2 and L2-3 levels.
View Article and Find Full Text PDFPeptide and dendritic cell vaccines activate the immune system against tumor antigens to combat brain tumors. Vaccines stimulate a systemic immune response by inducing both antitumor T cells as well as humoral immunity through antibody production to cross the blood-brain barrier and combat brain tumors. Recent trials investigating vaccines against peptides (ie, epithelial growth factor receptor variant III, survivin, heat shock proteins, or personalized tumor antigens) and dendritic cells pulsed with known peptides, messenger RNA or unknown tumor lysate targets demonstrate the potential for therapeutic cancer vaccines to become an important therapy for brain tumor treatment.
View Article and Find Full Text PDFThe neural crest, an embryonic stem-cell population, is a vertebrate innovation that has been proposed to be a key component of the 'new head', which imbued vertebrates with predatory behaviour. Here, to investigate how the evolution of neural crest cells affected the vertebrate body plan, we examined the molecular circuits that control neural crest development along the anteroposterior axis of a jawless vertebrate, the sea lamprey. Gene expression analysis showed that the cranial subpopulation of the neural crest of the lamprey lacks most components of a transcriptional circuit that is specific to the cranial neural crest in amniotes and confers the ability to form craniofacial cartilage onto non-cranial neural crest subpopulations.
View Article and Find Full Text PDFThe enteric nervous system of jawed vertebrates arises primarily from vagal neural crest cells that migrate to the foregut and subsequently colonize and innervate the entire gastrointestinal tract. Here we examine development of the enteric nervous system in the basal jawless vertebrate the sea lamprey (Petromyzon marinus) to gain insight into its evolutionary origin. Surprisingly, we find no evidence for the existence of a vagally derived enteric neural crest population in the lamprey.
View Article and Find Full Text PDFMembers of the Sox family of transcription factors play a variety of critical developmental roles in both vertebrates and invertebrates. Whereas SoxBs and SoxEs are involved in neural and neural crest development, respectively, far less is known about members of the SoxC subfamily. To address this from an evolutionary perspective, we compare expression and function of SoxC genes in neural crest cells and their derivatives in lamprey (Petromyzon marinus), a basal vertebrate, to frog (Xenopus laevis).
View Article and Find Full Text PDFMembers of the Sox (Sry-related high mobility group box) family of transcription factors play a variety of roles during development of both vertebrates and invertebrates. A marked expansion in gene number occurred during the emergence of vertebrates, apparently via gene duplication events that are thought to have facilitated new functions. By screening a macroarrayed library as well as the lamprey genome, we have isolated genes of the Sox B, D, E and F subfamilies in the basal jawless vertebrate, lamprey.
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