Epitope editing enables targeted immunotherapy of acute myeloid leukaemia.

ABSTRACT: Despite the considerable efficacy observed when targeting a dispensable lineage antigen, such as CD19 in B cell acute lymphoblastic leukaemia^1,2, the broader applicability of adoptive immunotherapies is hampered by the absence of tumour-restricted antigens^3-5. Acute myeloid leukaemia immunotherapies target genes expressed by haematopoietic stem/progenitor cells (HSPCs) or differentiated myeloid cells, resulting in intolerable on-target/off-tumour toxicity. Here we show that epitope engineering of donor HSPCs used for bone marrow transplantation endows haematopoietic lineages with selective resistance to chimeric antigen receptor (CAR) T cells or monoclonal antibodies, without affecting protein function or regulation. This strategy enables the targeting of genes that a

SUBMITTER: Casirati G 

PROVIDER: S-EPMC10499609 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature