B cell acute lymphoblastic leukaemias (B-ALLs) often express CD19, which is the target of chimeric antigen receptor-engineered T cells (CART-19 cells) that can be used therapeutically through adoptive transplantation into patients with B-ALL. However, ∼30% of patients with B-ALL receiving CART-19 cells relapse. Sotillo et al. found that resistance to CART-19 cells occurred through epitope loss that was mediated by exon 2 mutations and alternative splicing. Exon skipping resulted in the expression of a CD19 variant in which exon 2 is no longer expressed and CART-19 cells are no longer activated.
References
Sotillo, E. et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. (http://dx.doi.org/10.1158/2159-8290.CD-15-1020)
Rights and permissions
About this article
Cite this article
Alderton, G. Skipping out epitopes. Nat Rev Cancer 15, 699 (2015). https://doi.org/10.1038/nrc4053
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrc4053
