This week in cell therapy: Rare mechanism for cancer relapse after CAR-T reported, first results from Avrobio’s Fabry disease gene therapy trial and development of a novel technique to generate OPCs.
The news highlights:
Celyad to develop next-generation allogeneic CAR-T therapies
Rare mechanism for ALL relapse after CAR-T
Avrobio report mixed data from Fabry disease gene therapy trial
Novel technique to efficiently generate OPCs
Specialist biopharmaceutical company Celyad (Mont-Saint-Guibert, Belgium) have announced an exclusive agreement with Horizon Discovery Group (Cambridge, UK) to use its shRNA technology to develop a second non-gene-edited allogenic CAR-T candidate therapy. This comes shortly after the announcement of Celyad’s first-in-class CAR-T therapy, CYAD-101.
“We are excited to have the opportunity to leverage Horizon’s shRNA platform to further advance our pioneering approach to non-gene edited allogeneic CAR-T cells,” commented Christian Homsy, CEO of Celyad. “Celyad is committed to rapidly advancing its allogeneic program based on highly promising preclinical data which will be presented at SITC. These data provide proof of concept for our shRNA based non-gene-edited allogeneic approach.”
Findings from the University of Pennsylvania’s (PA, USA) Abramson Cancer Center have shown how a single, unknowingly engineered, leukemia cell led to the deadly recurrence of B-cell acute lymphoblastic leukemia (ALL). It is thought that the chimeric antigen receptor (CAR) lentivirus — infused into the patient to enter a T cell and train it to ‘hunt’ cancer — bound to a leukemic cell. This may have given the cell the ability to hide from the therapy by masking the protein CD19.
Lead author, Marco Ruella, assistant professor of Hematology-Oncology, remarked: “This is the first time in hundreds of patients treated at Penn and other institutions that we’ve observed this mechanism of relapse, and it provides important evidence that due to the delicate and complex manufacturing process any slight variation can have an impact on patient outcomes.”
Shares in Avrobio (MA, USA) have dropped by over 50% following the release of results from their ongoing Phase I clinical study of AVR-RD-01 — an ex vivo lentiviral gene therapy designed as a ‘one-and-done’ treatment to insert the GLA gene encoding a functional Î±-galactosidase A enzyme, which is deficient in Fabry disease.
While two patients show promise, and are reported to “demonstrate AGA enzyme activity above the diagnostic range for classic Fabry disease,” four patients have shown a drop in vector copy number — the average number of copies of the lentiviral-vector inserted gene integrated into a cell’s genome — in peripheral blood. These data have caused the share prices in Avrobio to plunge.
Case Western Reserve (OH, USA) researchers have developed a novel method to generate brain stem cells more efficiently. Large quantities of oligodendrocytes and oligodendrocyte progenitor cells (OPCs) were able to be generated from mouse embryonic stem cells and induced pluripotent stem cells. This will allow scientists to research genes and cellular processes thought to be associated with oligodendrocyte dysfunction without the need to produce mutant mice models.
“Making these specialized brain stem cells on a large scale at high purity from pluripotent stem cells gives us a powerful tool to study previously inaccessible normal and diseased tissues in the central nervous system,” concluded Paul Tesar, associate professor of genetics and genome sciences. “We applied our technology to genetic models of myelin disease, which resulted in the discovery of a chemical compound that helps diseased myelin-producing cells to survive.”
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