Figure 1
Prior cyclophosphamide conditioning results in 19mz+ T cell–mediated B-cell aplasias and eradication of systemic EL4(hCD19) tumors. (A) Schematic of retroviral construct encoding the 19mz and Pmz CARs. CD8 indicates CD8 leader sequence; scFv, single chain variable fragment; VH and VL, variable heavy and light chains; TM, transmembrane domain; LTR, long terminal repeat; SD, SA, splice donor and acceptor; and ψ, packaging element. (B) Persistent B-cell aplasias in C57BL6(mCD19−/− hCD19+/−) mice pretreated with cyclophosphamide followed by 19mz+ but not control Pmz+ T-cell therapy. 19mz+ T-cell therapy alone or cyclophosphamide alone failed to induce persistent B-cell aplasias. (C) Representative flow cytometry demonstrating B-cell aplasias in mice conditioned with cyclophosphamide followed by 19mz+ T-cell infusion at 4 weeks after T-cell infusion. (D) Cyclophosphamide conditioned EL4(hCD19) tumor-bearing C57BL6(mCD19−/− hCD19+/−) mice treated with 19mz+ T cells have enhanced survival compared with mice treated with 19mz+ T cells alone or control Pmz+ T cell–treated mice. All results are representative of at least 2 experiments.

Prior cyclophosphamide conditioning results in 19mz+ T cell–mediated B-cell aplasias and eradication of systemic EL4(hCD19) tumors. (A) Schematic of retroviral construct encoding the 19mz and Pmz CARs. CD8 indicates CD8 leader sequence; scFv, single chain variable fragment; VH and VL, variable heavy and light chains; TM, transmembrane domain; LTR, long terminal repeat; SD, SA, splice donor and acceptor; and ψ, packaging element. (B) Persistent B-cell aplasias in C57BL6(mCD19−/− hCD19+/−) mice pretreated with cyclophosphamide followed by 19mz+ but not control Pmz+ T-cell therapy. 19mz+ T-cell therapy alone or cyclophosphamide alone failed to induce persistent B-cell aplasias. (C) Representative flow cytometry demonstrating B-cell aplasias in mice conditioned with cyclophosphamide followed by 19mz+ T-cell infusion at 4 weeks after T-cell infusion. (D) Cyclophosphamide conditioned EL4(hCD19) tumor-bearing C57BL6(mCD19−/− hCD19+/−) mice treated with 19mz+ T cells have enhanced survival compared with mice treated with 19mz+ T cells alone or control Pmz+ T cell–treated mice. All results are representative of at least 2 experiments.

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