CD19 Antigen Occupancy on Cancer Cells with the CD19 Monoclonal Antibody Tafasitamab Improves the Activation, Antitumor Efficacy, and Safety Profile of CART19 Cell Therapy

How to integrate CD19 specific chimeric antigen receptor T cells with other CD19 targeting agents in diffuse large B‐cell lymphoma?

“…To experimentally address this hypothesis, Sakemura and colleagues cocultured CD19‐expressing JeKo‐1 cells with CD19‐CAR T cells in the presence of different concentrations of tafasitamab. Tafasitamab had a dose dependent inhibitory effect on CAR T cell killing, cell expansion and degranulation 68 . Similarly, the authors showed in vivo that concomitant administration of tafasitamab significantly inhibited tumor control by CD19‐CAR T cells in JeKo‐1‐bearing mice.…”

“…In vitro incubation of CD19-expressing lymphoma cell lines with tafasitamab significantly interfered with the detection of CD19 using fluorescence-labeled FMC63 monoclonal antibodies, the same clone from which the scFv of the three CAR T cells originates. 68 Similarly, Fitzgerald and colleagues recently showed in two patients that CD19 was undetectable by both flow cytometry and IHC in serial biopsies obtained before and up to 4 weeks after receiving tafasitamab treatment. 69 The ability to detect CD19 expression by IHC or flow cytometry after anti-CD19 therapies is most likely dependent on the specific antibodies used.…”

“…Tafasitamab had a dose dependent inhibitory effect on CAR T cell killing, cell expansion and degranulation. 68 Similarly, the authors showed in vivo that concomitant administration of tafasitamab significantly inhibited tumor control by CD19-CAR T cells in JeKo-1-bearing mice. Interestingly, once previous treatment with tafasitamab stopped before CAR T cell administration, it did not interfere with the antitumor effect of CAR T cells that was increased in their model.…”

“…Interestingly, once previous treatment with tafasitamab stopped before CAR T cell administration, it did not interfere with the antitumor effect of CAR T cells that was increased in their model. 68 Collectively, this preclinical and clinical evidence suggests that tafasitamab might in fact interfere with CD19-recognition by CAR T cell when still present at biologically active concentrations. The clinical relevance for the in vivo application of currently available CAR T cells after CD19-targeting antibodies is unknown.…”

“…This is a situation where different CD19‐targeting agents compete for its detection (Figure 2, right panel) with CD19 persistence at the cell surface. In vitro incubation of CD19‐expressing lymphoma cell lines with tafasitamab significantly interfered with the detection of CD19 using fluorescence‐labeled FMC63 monoclonal antibodies, the same clone from which the scFv of the three CAR T cells originates 68 . Similarly, Fitzgerald and colleagues recently showed in two patients that CD19 was undetectable by both flow cytometry and IHC in serial biopsies obtained before and up to 4 weeks after receiving tafasitamab treatment 69 .…”