Unedited allogeneic iNKT cells show extended persistence in MHC-mismatched canine recipients.

ABSTRACT: Allogeneic invariant natural killer T cells (allo-iNKTs) induce clinical remission in patients with otherwise incurable cancers and COVID-19-related acute respiratory failure. However, their functionality is inconsistent among individuals, and they become rapidly undetectable after infusion, raising concerns over rejection and limited therapeutic potential. We validate a strategy to promote allo-iNKT persistence in dogs, an established large-animal model for novel cellular therapies. We identify donor-specific iNKT biomarkers of survival and sustained functionality, conserved in dogs and humans and retained upon chimeric antigen receptor engineering. We reason that infusing optimal allo-iNKTs enriched in these biomarkers will prolong their persistence without requiring MHC ablation, high-i

SUBMITTER: Rotolo A 

PROVIDER: S-EPMC10591065 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature