Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell.
Marco RuellaJun XuDavid M BarrettJoseph A FraiettaTyler J ReichDavid E AmbroseMichael KlichinskyOlga ShestovaPrachi R PatelIrina KulikovskayaFarzana NazimuddinVijay G BhojElena J OrlandoTerry J FryHans BitterShannon L MaudeBruce L LevineChristopher L NoblesFrederic D BushmanRegina M YoungJohn SchollerSaar I GillCarl H JuneStephan A GruppSimon F LaceyJ Joseph MelenhorstPublished in: Nature medicine (2018)
We report a patient relapsing 9 months after CD19-targeted CAR T cell (CTL019) infusion with CD19- leukemia that aberrantly expressed the anti-CD19 CAR. The CAR gene was unintentionally introduced into a single leukemic B cell during T cell manufacturing, and its product bound in cis to the CD19 epitope on the surface of leukemic cells, masking it from recognition by and conferring resistance to CTL019.
Keyphrases
- acute myeloid leukemia
- multiple sclerosis
- nk cells
- induced apoptosis
- bone marrow
- low dose
- case report
- rheumatoid arthritis
- gene expression
- signaling pathway
- cell proliferation
- oxidative stress
- cell death
- systemic lupus erythematosus
- cancer therapy
- transcription factor
- dna methylation
- disease activity
- endoplasmic reticulum stress
- smoking cessation