Fig. 5

Trogocytosis-associated CAR-T resistance can be partially offset by adoptively administering CAR-T of antigen-density-matched sensitivity. a–c Short-term killing (4 h) of high or low-sensitivity CAR-T cells against U87 cells with varied antigen density levels. Both high and low-sensitivity CAR-T cells showed similar cytotoxicity against high-antigen density U87 cells, while high sensitivity CAR-T cells exhibited stronger cytotoxicity against median and low-antigen density U87 cells (n = 4 independent samples). d–f Long-term killing (24 h) of high or low-sensitivity CAR-T cells against U87 cells with different antigen density levels. Still, low-sensitivity CAR-T cells demonstrated weak cytotoxicity against low-antigen density U87 cells. High and low-sensitivity CAR-T showed similar cytotoxicity against medium and high-antigen density U87 cells in the long-term killing assay (n = 4 independent samples). g Representative bioluminescent image of tumor burden of U87 cells with EGFRvIII low density, followed by the treatment with high (green) or low-sensitivity (red) CAR-T cells. NC, peripheral blood T cells. h, i Bioluminescence intensity (total flux) and Kaplan–Meier analysis of mice in g, n = 5–7 per group. j Representative bioluminescent image of tumor burden using U87 cells with EGFRvIII high density, followed by the treatment with high (red) or low-sensitivity (green) CAR-T cells. k, l Bioluminescence intensity (total flux) and Kaplan–Meier analysis of mice in j, n = 5–7 per group. Data are represented as mean ± SD, unpaired Student’s t test, *P < 0.05; **P < 0.01; ***P < 0.001, ****P < 0.0001