Publications by authors named "V Allain"

Article Synopsis
  • CAR-T therapy is a new way to treat blood cancers and is being looked at for other diseases and issues like solid tumors and aging.
  • Traditional methods to create these CAR-T cells can hurt the cells or cause problems, making them less safe and effective.
  • A new method called hydroporation helps make more healthy CAR-T cells quickly and efficiently, which could lead to better treatments for patients.
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Article Synopsis
  • Immune effector cell-associated neurotoxicity syndrome (ICANS) is a serious complication of CD19-targeted CAR T-cell therapy, and early prediction of patients at risk is crucial for tailored management.
  • Elevated serum neurofilament light chain (NfL) levels are linked to the severity of ICANS, with higher levels indicating greater neuroaxonal injury.
  • In a study of 150 patients, those with elevated NfL (>75 pg/mL at leukapheresis or >58 pg/mL at infusion) were significantly more likely to develop severe ICANS, suggesting that NfL could be a vital predictive marker for neurotoxicity in CAR T-cell therapy.
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We present a TALEN-based workflow to generate and maintain dual-edited (IL-15/TGFβR2) iPSCs that produce enhanced iPSC-derived natural killer (iNK) cells for cancer immunotherapy. It involves using a cell lineage promoter for knocking in (KI) gene(s) to minimize the potential effects of expression of any exogenous genes on iPSCs. As a proof-of-principle, we KI IL-15 under the endogenous B2M promoter and show that it results in high expression of the sIL-15 in iNK cells but minimal expression in iPSCs.

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NK cells express activating receptors that signal through ITAM-bearing adapter proteins. The phosphorylation of each ITAM creates binding sites for SYK and ZAP70 protein tyrosine kinases to propagate downstream signaling including the induction of influx. While all immature and mature human NK cells co-express SYK and ZAP70, clonally driven memory or adaptive NK cells can methylate genes and signaling is mediated exclusively using ZAP70.

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Article Synopsis
  • CAR-T therapy is revolutionary for treating blood cancers and is being explored for other conditions, but faces manufacturing and safety issues.
  • Traditional methods for cell engineering can lead to random gene placement or cellular damage, which can affect therapy effectiveness.
  • Hydroporation is introduced as a more effective method, yielding higher quality CAR-T cells with better growth and performance, and can be scaled up quickly for large production needs.
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