Enhanced rejection of colon carcinomas in scid mice by scFv-anti-erbB2-CD28-ζ–transduced T cells.

(A) Early treatment of erbB2⁺ tumors. Growth of the erbB2⁺ human COLO 205 colon carcinoma cells or mouse MC-38-erbB2 colon adenocarcinoma cells (right flank) and erbB2⁻ 24JK mouse sarcoma cells or MC-38 cells (left flank), respectively, were injected subcutaneously in groups of 5 to 10 scid mice (as described in “Materials and methods”). Mice were injected intravenously with 2 doses (5 × 10⁶) of BALB/c T cells transduced with the pLXSN vector alone (■), scFv-anti-erbB2-ζ chimera (●), or scFv-anti-erbB2-CD28-ζ chimera (○) on day 0 and day 1 after tumor inoculation. The number of tumor eradications is shown in parentheses. Growth of the COLO 205 and 24JK tumors was also evaluated in scid mice receiving no T-cell transfer (▪). (B) Delayed treatment of 3-day established erbB2⁺tumors. The subcutaneous growth of erbB2⁺ COLO 205 tumors (right flank) or erbB2⁻24JK tumors (left flank, not shown) in groups of 5 to 10 scid mice. Mice were injected intravenously with a single dose (10⁷) of BALB/c T cells transduced with the pLXSN alone (■), scFv-anti-erbB2-ζ chimera (●), or scFv-anti-erbB2-CD28-ζ chimera (○) on day 3 after tumor inoculation. Growth of the COLO 205 tumor was also evaluated in scid mice receiving no T-cell treatment (▪). (C) Dose response of transduced T cells. The subcutaneous growth of erbB2⁺ COLO 205 tumors in groups of 10 scid mice. Mice were injected intravenously with a single dose of 10⁷ (●), 10⁶ (▪), or 10⁵ (▴) T-scFv-anti-erbB2-ζ cells or 10⁷(○), 10⁶ (■), or 10⁵ (▵) T-scFv-anti-erbB2-CD28-ζ cells on day 1 after tumor inoculation. Growth of the COLO 205 tumor was evaluated in scid mice receiving no T-cell treatment (♦). For all experiments, results are represented as the mean tumor size (mm²) ± SEM. Arrows depict the days of T-cell transfer. COLO 205 tumor growth inhibited by T-scFv-CD28-ζ and T-scFv-ζ receptors was statistically compared at similar T-cell doses by Mann-Whitney test (*P < .05, **P < .0001).