Figure 7.
Inhibition of T cells by the peptide SLP76pTYR allows tumor clearance without inducing GVHD
(A) Purified WT CD8+ and CD4+ T cells were mixed (1X106 total) at a 1:1 ratio, and transduced with viruses containing SLP76pTYR or empty vector, then transplanted along with 1X105 B-ALL- luc cells and 5 × 106 T cell-depleted bone marrow cells into irradiated BALB/c mice. Host BALB/c mice were imaged using IVIS 200 3 times a week. Group one received 10 × 106 T cell-depleted bone marrow alone (TCDBM). Group two received 10X106TCDBM along with 1X105 B-ALL-luc cells (TCDBM + B-ALLluc). The third group was transplanted with 10X106TCDBM and a 1:1 ratio of purified WT CD8+ and CD4+ T cells (1X106 total) along with 1X105 B-ALL-luc cells (TCDBM + B-ALLluc + WT CD8+CD4). Group four received 10X106TCDBM and a 1:1 ratio of purified WT CD8+ and CD4+ T cells (1X106 total) transduced with control viruses along with 2X105 B-ALL-luc cells (TCDBM + B-ALLluc + Empty CD8+CD4). Group five received 10X106TCDBM, a 1:1 ratio of purified WT CD8+ and CD4+ T cells (1X106 each) transduced with SLP76pTYR-carrying viruses, and with 1X105 B-ALL-luc cells (TCDBM + B-ALLluc + SLP76pTYR virus CD8+CD4).
(B–D) (B) The mice were monitored for survival, (C) body weight changes, and (D) clinical score for 40 days post BMT. For weight changes and clinical score, one representative of 2 independent experiments is shown (n = 3 mice/group for BM alone; n = 5 experimental mice/group for all three group).
(E) Quantitated luciferase bioluminescence of tumor growth.
(F) Tumor incidence for each of the experimental groups.
Statistical analysis for survival and clinical score was performed using log rank test and two-way ANOVA, respectively. Note: Controls are naive for tumor, but transplanted with 10 × 106T cell depleted bone marrow alone (TCDBM) and used as a negative control for BLI.