Allogene Therapeutics Announces Publication of Industry-Advancing Case Study on Chromosomal Rearrangement in Molecular Therapy
- Publication Reviews Investigation of a Chromosomal Rearrangement Observed in a Single Patient Receiving Gene-Edited Allogeneic CAR T Treatment for Large B Cell Lymphoma
- Case Reveals Normal T Cell Biology Occurring in CAR T Cells, Including Notable Finding of Continued Chromosomal Rearrangement in Mature Lymphocytes
- Results Reinforce Previous Findings that the Rearrangement was Not Related to Cell Manufacturing or Gene Editing, and Not Associated with Clinical Significance
The development of “off-the-shelf” (allogeneic) CAR T products that utilize cells from healthy donors have the potential to make CAR T therapies scalable and accessible to more patients. Gene editing is a common technique deployed to create allogeneic CAR T cells and other engineered cell therapy candidates. Gene editing has the potential to induce chromosomal inversions as a consequence of post cleavage genetic recombination.
The Company’s case report details a chromosome 14 inversion in a patient treated with gene edited cells. Initial caution surrounding this case led to a
“As the leader in the development of allogeneic CAR T cell treatments, we understand our responsibility to patients as well as the important role we play in advancing this rapidly developing field,” said
The investigation concerned a population of allogeneic CAR T cells containing a chromosome 14 inversion that was incidentally detected 47 days following the administration ALLO-501A. The rearrangement was not detectable in the manufacturing lots used to treat the patient or in any other lot manufactured by Allogene. Thorough molecular analysis of the inversion, which was distantly located from TALEN gene edited or lentiviral vector insertion sites, revealed that the breakpoints mapped to genomic sites well-known to be used by B and T cell recombination pathways, indicating that the inversion was a result of normal T cell biology. A broad investigation was undertaken, and the inversion was not detectable in any other patient sample assessed by Allogene from this and other trials. The report further concluded that the inversion spontaneously occurred post ALLO-501A infusion. There was no evidence that the expansion of this clone was the consequence of the inversion, and no clinical significance was attributed to the event.
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This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the ability to advance the ALPHA2 trial of ALLO-501A; the final results of the investigation, including the clinical significance of the chromosomal abnormality and any relationship to gene editing or manufacturing; the ability to manufacture and develop allogeneic CAR T therapies for cancer; and the potential benefits of AlloCAR T. Various factors may cause differences between Allogene’s expectations and actual results as discussed in greater detail in Allogene’s filings with the
AlloCAR T™ is a trademark of
TALEN® is a registered trademark of
Allogene’s AlloCAR T™ programs utilize the Cellectis TALEN® technologies. ALLO-501 and ALLO-501A are anti-CD19 products being jointly developed under a collaboration agreement between
Allogene Media/Investor Contact:
Chief Communications Officer
(714) 552-0326
Christine.Cassiano@allogene.com

Source: Allogene Therapeutics, Inc.