Figure 6.
Anti-tumor activities of lentiviral-transduced T cells tested in vitro and in mouse tumor models. (A) CAR expression of RNA-T cells (RNA-T) or CD3/CD28 Dynabead T cells (Beads) lentiviral-transduced with an ErbB2 CAR (4D5-BBZ). (B) Summary of three independent experiments for detection of CD107a in 4D5-BBZ CAR transduced (TD) T cells stimulated by ErbB2-positive tumor lines SK-OV3, MCF7, and MDA231, using the tumor line MDA468 and non-transduced (NO TD) T cells as negative controls. (C) Cytokine production of T cells stimulated by ErbB2-positive tumor lines SK-OV3, MCF7, and MDA231 and an ErbB2-negative tumor line MDA468. (D) Mice (n = 5) were subcutaneously implanted with SK-OV3-CBG tumor cells (5 × 106 cells/mouse) on the flank. The mice were treated with T cells (i.v.) on day 18 after SK-OV3-CBG tumor inoculation. A dose of 1 × 106 CAR+ T cells from either RNA-T cells (RNA-T 4D5-BBZ) or CD3/CD28 Dynabead T cells (Beads 4D5-BBZ) was given as a single injection. Mice treated with non-transduced RNA-T cells (RNA-T only) served as controls. Animals were imaged at the indicated time. (E) CD19 CAR lentiviral-transduced T cells generated by OKT3/IL-2 (OKT3), CD3/CD28 Dynabead (Beads) or OKT3-28BB/CD86/4-1BBL co-electroporated RNA (RNA-T) were compared in the Nalm6 leukemia model. Leukemia was established in NSG mice (n = 3 per group) by i.v. injection with 5 × 106 Nalm6-CBG cells. Beginning on day 7, 1 × 106 CD19-BBZ lentivirus-transduced T cells were injected (i.v.). BLI was conducted at the time indicated