Chimeric antigen receptor (CAR) T-cell therapy is highly effective in the treatment of B-cell acute lymphoblastic leukemia (ALL) or B-cell lymphoma, providing alternative therapeutic options for patients who failed to respond to conventional treatment or relapse. Moreover, it can bridge other therapeutic strategies and greatly improve patient prognosis, with broad applicable prospects. Even so, 30–60% patients relapse after treatment, probably due to persistence of CAR T-cells and escape or downregulation of CD19 antigen, which is a great challenge for disease control. Therefore, understanding the mechanisms that underlie post-CAR relapse and establishing corresponding prevention and treatment strategies is important. Herein, we discuss post-CAR relapse from the aspects of CD19-positive and CD19-negative and provide some reasonable prevention and treatment strategies.
Patterned poly(N-isopropylacrylamide) (PNIPAAm) brushes were fabricated on oxidized silicon wafers by surface-initiated atom transfer radical polymerization of N-isopropylacrylamide from a micropatterned initiator. The patterned surface initiator was prepared by microcontact-printing octadecyltrichlorosilane and backfilling with 3-(aminopropyl)triethoxysilane followed by amidization with 2-bromo-2-methylpropionic acid. XPS and FTIR confirmed the chemical structure of the surface initiator and the PNIPAAm brushes. Surface analysis techniques, including ellipsometry, contact angle goniometry, and X-ray reflectometry (XRR), were used to characterize the thickness, roughness, hydrophilicity, and density of the polymer brushes. Tapping-mode AFM imaging confirmed the successful patterning of the PNIPAAm brushes on the oxidized silicon substrates. Variable temperature ellipsometry indicated that the lower critical solution temperature of the hydrated PNIPAAm brush was broad, occurring over the range of 20-35 degrees C. A solvatochromic fluorophore, 6-propionyl-2-dimethylaminonaphthalene (Prodan), in the PNIPAAm brush layers yielded a very similar emission to that in DMF, which can be attributed to the similarity of their chemical structures. Fluorescence microscopy further proved the successful patterning of the polymer brushes and suggested that the Prodan is localized in the patterned PNIPAAm brushes and excluded from the surrounding octadecyltrichlorosilane regions.
The electrical conductivity of sintered samples of (CeO 2 ) 1Ϫx (SmO 1.5 ) x (0.10 р x р 0.40) in air was investigated systematically as a function of temperature between 240 and 1000°C by using two-probe ac impedance technique. The relative contribution of the grain interior ͑lattice͒ and grain boundaries to the overall resistance, is discussed in detail in relation with the grain boundary effect. The maximum lattice conductivity observed ͑at 600°C͒ was 2 S/m for Ce 0.9 Sm 0.1 O 1.95 . With an increase in samarium concentration, the grain interior conductivity decreases gradually, but the grain boundary conductivity increases dramatically. The two opposite effects lead to a maximum ( t , 600°C ϭ 1 S/cm͒ in the overall conductivity at x ϭ 0.2. A linear relationship between the association enthalpy of the defect cluster, ͓Sm Ce Ј Ϫ V O •• ͔, and x 1/3 was proposed.
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