Here we show that disruption of SPPL3 caused CD19 hyperglycosylation which impairs the binding of anti-CD19 antibodies and impairs CAR T cell activation, thus enabling resistance to CAR therapy. We identify that hyperglycosylation of an asparagine residue proximal to the CAR binding epitope is directly responsible for enabling resistance.

Reference
Pubmed: Heard A, Landmann JH, Hansen AR, Papadopolou A, Hsu YS, Selli ME, Warrington JM, Lattin J, Chang J, Ha H, Haug-Kroeper M, Doray B, Gill S, Ruella M, Hayer KE, Weitzman MD, Green AM, Fluhrer R, Singh N. Antigen glycosylation regulates efficacy of CAR T cells targeting CD19. Nat Commun. 2022 Jun 11;13(1):3367. doi: 10.1038/s41467-022-31035-7.